Can epigenetics have positive impact on the genes are development?

I know that epigenetics have capacity to affect and degrade the genes thereby inducing problems/illness/degradation in body functions.

Can they also make better genes or have positive impact on genes or body? If yes, can someone give some examples?

First, let me qualify the idea of "problematic" epigenetic modifications by saying that the impact of a modification on an organism is often dependent on the environment. That is to say that outcome is dependent on the interaction of genetics (or epigenetics) and the environment in which the associated genes are expressed; e.g. a mutation or modification that confers an advantage in a nutrient-limiting environment may be detrimental when nutrients are plentiful.

Second, it is helpful to think of epigenetic modifications as reversible switches rather than entities that "degrade the genes". In fact, the etymology of "epigenetic" implies that such changes work at a level above that of the gene sequence, i.e. gene expression. Canonically, DNA methylation and histone modifications (acetylation and methylation) modify the expression of a gene by regulating the ability of RNA polymerase to access that gene, either by directly influencing transcription factor binding or modulating the associations of nucleosomes and DNA. Read up on facultative heterochromatin.

As for examples, I point you to a set of papers that show associations between human starvation, epigenetics, and disease / mortality outcomes across generations.

DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

[DNA methylation] at six CpGs, including at previously [serum triglyceride]-associated CpGs at TXNIP and ABCG1, mediated the association between famine exposure and [serum triglyceride]. [DNA methylation] at these CpGs was likewise associated with the expression of genes implicated in cell growth and energy metabolism.

Note that the authors present caveats to their analyses in the discussion. The New York Times also covered this publication.

Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons

This publication is essentially a replication of the published works concerning transgenerational epigenetics in the Överkalix cohort. They give a concise summary of how epigenetic changes caused by environmental stress may be heritable:

An intriguing aspect of these studies is the conjecture that an epigenetic pathway, carrying information across generations, may open up just before puberty, during the so-called slow growth period (SGP). Pre-puberty may be one of several “windows” for germline reprogramming in response to nutritional signals. A number of mechanisms for transmission across generations have been suggested, usually involving DNA methylation, chromatin formation or small noncoding RNAs. After fertilization, in the preimplantation embryo, epigenetic modifications acquired early in life are then usually erased, but not fully. Imprinting on specific loci may resist the post fertilization wave of reprogramming, eventually causing changes in offspring phenotype that are not driven by changes of the DNA sequence.

If you're looking for more examples, research genomic imprinting.

Epigenetics: How You Can Change Your Genes And Change Your Life

E pigenetics is a relatively new branch of genetics that has been heralded as the most important biological discovery since DNA. Until recently, it was believed you were stuck with the genes you were born with. But now it’s known that your genes get turned on and off and are expressed to greater or lesser degrees depending on lifestyle factors. Let’s take a look at what epigenetics is, how it works, and what you can do to improve your chances in the health lottery.

What Is Epigenetics?

The “epi” in epigenetics is derived from the Greek word meaning “above” or “over.” Epigenetics is defined as the study of any process that alters gene activity without changing the DNA sequence. More simply, it is the study of gene expression — how external factors turn genes on and off, and up and down.

The Human Genome Project has identified 25,000 genes in human DNA. DNA is widely regarded as the code the body uses to build and rebuild itself. But genes themselves need instructions for what to do, and where and when to do it.

Epigenetic modifications, also called “tags,” provide the instructions. Several of these tags have been discovered, but the two main ones involve methyl groups (made of carbon and hydrogen) and histones (a type of protein). To imagine how tags work, think of a gene as a lamp. Methyl groups act as an on-off switch that turn a gene on or off. Histones, on the other hand, act like a dimmer switch, regulating gene activity up or down. It’s thought that we have four million of these switches that are triggered by lifestyle and environmental factors.

Via: Vitalinka | Shutterstock

Identical Twins Provide Clues

The study of identical twins, who have the same genetic material, has provided researchers with a unique window into epigenetic changes. The effect of lifestyle factors on genes is so strong that genes of identical twins can diverge significantly during the course of their lives. Research shows that as identical twins age, especially ones that spend the most time apart, their genes become less alike.

You might expect that identical twins would have similar health histories, yet they exhibit vastly different incidences of many diseases including mental disorders such as alcoholism, Alzheimer’s, bipolar disorder, and schizophrenia and physical disorders such as diabetes, cancer, Crohn’s disease, and rheumatoid arthritis. This is due to epigenetic drift — a change in gene expression over time.

Lifestyle Factors Affect Your Genes

Dr. Rudolph Tanzi is a professor of neurology at Harvard University Medical School. Among his many accomplishments, he co-discovered three genes that cause early onset familial Alzheimer’s disease. Along with Dr. Deepak Chopra, global leader in the field of mind-body medicine, he co-authored Super Genes: Unlock the Astonishing Power of Your DNA for Optimum Health and Well-Being.

In Super Genes they write: ”Only 5% of disease-related gene mutations are fully deterministic, while 95% can be influenced by diet, behavior, and other environmental conditions. Current models of well-being largely ignore genes, yet studies have shown that a program of positive lifestyle changes alter 4,000 to 5,000 different gene activities.” Tanzi and Chopra go on to say: “You are not simply the sum total of the genes you were born with. You are the user and controller of your genes, the author of your biological story. No prospect in self-care is more exciting.”

This is exciting news! It means that you’re not at the mercy of your genetic makeup at birth. You actually have a great deal of control over your health and your future no matter what genetic hand you have been dealt. The field of epigenetics is in its infancy and there is still much to learn, but so far the evidence shows that there are many fundamental lifestyle factors that can alter gene expression.

Epigenetics explains why twins with similar DNA can face very different health issues. Via: Werner Heiber | Shutterstock.

Diet, Sleep And Exercise Modulate Gene Expression

Not surprisingly, diet can affect the health of your DNA. A diet high in refined carbohydrates that promotes high blood glucose attacks your DNA. On the other hand, compounds like sulforaphane (found in broccoli), curcumin (turmeric), epigallocatechin gallate (green tea), and resveratrol (wine) can slow or potentially reverse DNA damage.

Inadequate sleep also disrupts genetic activity. A team of researchers that included sleep science and genetics experts examined the influence of sleep on gene function and discovered that just a single week of insufficient sleep altered the activity of over 700 genes.

It’s well accepted that physical exercise is one of the best things you can do for your overall health and mental well-being. Now there’s evidence that physical exercise can positively affect gene expression. A recent study of the brains of elderly mice found 117 genes that were expressed differently in the brains of animals that ran regularly, compared to those that were sedentary.

So Do Stress, Relationships, And Thoughts

Not only do tangible factors like diet, sleep, and exercise affect your genes, so do intangibles like stress, your relationships with others, and your thoughts. One of the most powerful stress reduction techniques, mindfulness meditation, turns down the expression of pro-inflammatory genes thus reducing inflammation. Chronic inflammation is an underlying cause of seven of the top ten leading causes of death including cancer, heart disease, diabetes, and Alzheimer’s.

You might expect that you’d have to meditate for years to change gene expression sufficiently, but measurable changes have been observed in as little as eight hours of meditation. However, these effects were stronger in experienced meditators than in those new to the practice.

Dr. Dawson Church is an award-winning author whose bestselling book, Genie in Your Genes: Epigenetic Medicine and the New Biology of Intention, has been hailed as a breakthrough in the field of epigenetics. In his book, Church cites over 400 scientific studies that show how intangibles like the expression of gratitude, acts of kindness, optimism, and mind-body healing techniques like the Emotional Freedom Technique positively affect the expression of genes. And just as in the meditation study, these epigenetic benefits were often experienced immediately.

It’s not only positive habits that affect your genes though. So do the bad ones. Substance abuse, addictions, inactivity, malnutrition, and exposure to toxins negatively affect the way your genes express themselves. Researchers have found that emotional factors such as trauma and stress can activate harmful epigenetic changes.

There are numerous diseases thought to have an epigenetic component including asthma, Alzheimer’s, cancer, diabetes, immune disorders, kidney disease, glaucoma, muscular dystrophy, and pediatric syndromes as well as many psychiatric disorders including autism, schizophrenia, and bipolar disorder. In 2008, the U.S. National Institutes of Health committed to investing $190 million into epigenetics research to hopefully find new and better ways to treat these diseases.

Dr. Randy Jirtle (left) was able to radically change the genetic expression of the offspring of genetically similar yellow agouti (Avy) mice (right) just by manipulating their diet using methyl donors (i.e. choline, betaine, folic acid, and vitamin B12). Via:

Epigenetics Changes Last For Generations

One of the most amazing and controversial discoveries is that epigenetic changes don’t stop with you. Epigenetic signals from the environment can be passed from one generation to the next, sometimes for several generations, without changing a single gene sequence.

According to Dr. Mitchell Gaynor, author of The Gene Therapy Plan: Taking Control of Your Genetic Destiny with Diet and Lifestyle, “One’s DNA, it turns out, is not fixed at all, and outside influences — lifestyle, thinking, nutrition, nurturing, and environmental factors — actually influence the way genes express in our bodies. In fact, we now know that genetic expression comes from generations before us and will continue for the generations after us. Today, the debate is not nature versus nurture. We have evolved into understanding that it is nature plus nurture.”

Dr. Randy Jirtle is a pioneer in epigenetic research. He holds two U.S. patents on imprinted genes and has published more than 170 peer-reviewed articles. “Epigenetics is proving we have some responsibility for the integrity of our genome,” Jirtle says. “Before, genes predetermined outcomes. Now everything we do — everything we eat or smoke — can affect our gene expression and that of future generations. Epigenetics introduces the concept of free will into our idea of genetics.” In fact, some of his research shows that epigenetic changes may endure in at least four subsequent generations.

The implications of this are profound. What you do today could affect the health and behavior of your grandchildren just as what your grandparents did affects your health today.

Epigenetics is a complex topic with potentially far-reaching consequences. To bring the concepts involved down to earth, I recommend this slightly offbeat video from SciShow. It explains how epigenetics works using the analogy of two hypothetical twins separated at birth and raised under very different circumstances.

This article was brought to you by Deane Alban, a health information researcher, writer, and teacher for over 25 years. For more helpful articles about improving your cognitive and mental health, visit today.


For decades, scientists have known the basic structure of our DNA, the building blocks that make up our genes. Although nearly every cell in the human body has the same set of genes, why is it that different types of cells, such as those from brain or skin, look and behave so differently?

The answer is epigenetics, a rapidly growing area of science that focuses on the processes that help direct when individual genes are turned on or off. While the cell&rsquos DNA provides the instruction manual, genes also need specific instructions. In essence, epigenetic processes tell the cell to read specific pages of the instruction manual at distinct times.

Some epigenetic changes are stable and last a lifetime, and some may be passed on from one generation to the next, without changing the genes.

Several epigenetic processes involve chemical compounds that attach, or bind, to DNA or to proteins that package the DNA within cells called histones. When a chemical compound binds to DNA, certain genes switch on or off, selecting which proteins are made.

For example, the epigenetic process of DNA methylation involves the binding of a chemical compound called a methyl group to certain locations on the DNA. This binding changes the structure of DNA, making genes more or less active in their role of making proteins.

Another process called histone modification involves chemical compounds that bind to histone proteins. Ribonucleic acids, or RNAs, are also present in cells and can participate in epigenetic processes that regulate the activity of genes.

DNA methylation and histone modification are normal processes within cells and play a role in development, by instructing stem cells, or cells capable of turning into more specialized cells, like brain or skin cells.

Epigenetic processes are particularly important in early life when cells are first receiving the instructions that will dictate their future development and specialization. These processes can also be initiated or disrupted by environmental factors, such as diet, stress, aging, and pollutants.

In 2005, a team of Italian researchers provided the first concrete evidence for the role of environmental epigenetics in explaining why twins with the same genetic background can have vastly different disease susceptibilities. 1 The researchers showed that, at birth, pairs of identical twins have similar epigenetic patterns, including DNA methylation and histone modifications.

However, over time, the epigenetic patterns of individuals become different, even in twins. Since identical twins are the same genetically, the differences are thought to result from a combination of different environmental influences that each individual experiences over a lifetime.

What is NIEHS Doing?

Investigating the effects of the environment on the epigenetic regulation of biological processes and disease susceptibility is a goal in the NIEHS 2012-2017 Strategic Plan.

NIEHS is currently supporting epigenetics research that is accelerating the understanding of human biology and the role of the environment in disease. These discoveries may lead to the development of new ways to prevent and treat diseases for which the environment is believed to be a factor.

NIEHS at the forefront of epigenetics research

In 2003, NIEHS-supported researchers made an important discovery that demonstrated the role of environmental epigenetics in development and disease. 2 They used the agouti mouse in their study. The mouse has an altered version of the agouti gene, which causes them to be yellow, obese, and highly susceptible to developing diseases, such as cancer and diabetes.

The researchers fed the mice a diet rich in methyl groups. Through epigenetic processes, the methyl groups attached to the mother&rsquos DNA, and turned off the agouti gene. As a result, most of the offspring were born lean and brown, and no longer prone to disease.

This study was the first to demonstrate that it is not just our genes that determine our health, but also our environment and what we eat.

NIEHS-supported researchers establish epigenomic reference maps

While researchers have known, for quite some time, the sequence of DNA that make up all human genes, collectively known as the genome, the same could not be said for the human epigenome, until recently. The epigenome refers to all of the chemical compounds added to the genetic material of an organism that regulate its function.

NIEHS and the National Institute on Drug Abuse (NIDA) co-led a national effort, through the NIH Roadmap Epigenomics Program , to create a series of epigenomic maps representing locations on the DNA where chemical compounds attached in more than 100 different tissue and cell types, including blood, lung, heart, gastrointestinal tract, brain, and stem cells. The groundbreaking work was featured in a 2015 article in the journal Nature. 3

By comparing the epigenomic map of a healthy cell or tissue, with the map of the same cell or tissue after an environmental exposure or in relation to a specific disease, NIEHS scientists can better understand how the environment affects genes through epigenetic processes. The epigenomic maps are available to the entire scientific community through the Washington University Epigenome Browser .

Grantees study link between environmental pollution and disease

NIEHS-supported researchers at Harvard T.H. Chan School of Public Health have shown that human exposure to environmental air pollutants and toxic metals, such as arsenic, can cause damage to cells that may lead to cardiovascular disease. The research team has been tracking abnormalities in blood, as well as epigenetic changes, which may serve as indicators, or markers, of exposure to air pollution and toxic metals at levels that can increase the risk of cardiovascular disease, particularly in elderly men. These markers may help in the early detection and prevention of cardiovascular and other diseases. 4 , 5

Grantees at Beth Israel Deaconess Medical Center used epigenetics to define the link between environmental exposure to smoke, mercury, and lead, and reproductive outcomes, such as preterm birth. 6 , 7 Their results are important, since more than one in 10 infants worldwide is born prematurely, increasing their chances of having health problems later in life. 8 The study also found that epigenetic changes may serve as markers for maternal chemical exposure during pregnancy.

Scientists investigate epigenetic control of genes involved in cancer

NIEHS scientists in the Epigenetics and Stem Cell Biology Laboratory are examining how epigenetic mechanisms influence normal cell development, and contribute to biological processes involved in breast cancer and immune function. To date, they have uncovered many details of how the protein complex Mi-2/NuRD controls genes involved in breast cancer. Mi-2/NuRD is found in the nucleus of cells and includes enzymes that affect histone modifications that regulate gene activity.

The research is helping to identify what genes are regulated by the complex and how the complex alters epigenetic processes that may contribute to disease. Understanding the underlying mechanisms of disease may lead to the development of new methods to diagnose, prevent, and treat diseases, such as breast cancer, in the future.

Researchers unravel role of epigenetics in development, inheritance, and disease

NIEHS-supported researchers have found that early-life exposure to nutritional and dietary factors, maternal stress, and environmental chemicals can increase the likelihood of developing disease and poor health outcomes later in life. In addition, some of the effects of these exposures can be passed down for multiple generations, even after the original exposure has been removed, through a process known as transgenerational inheritance.

Researchers in the NIEHS Transgenerational Inheritance in Mammals After Environmental Exposure (TIME) Program are using mice and rats to investigate how transgenerational inheritance occurs after exposure to environmental exposures, whether the process is different in males and females, and when in development these events are most likely to occur. Understanding how transgenerational inheritance of effects from exposures occur in animals may shed light on similar processes in humans.

Correcting Popular Misrepresentations of Science

Until recently, the influences of genes were thought to be set, and the effects of children’s experiences and environments on brain architecture and long-term physical and mental health outcomes remained a mystery. That lack of understanding led to several misleading conclusions about the degree to which negative and positive environmental factors and experiences can affect the developing fetus and young child. The following misconceptions are particularly important to set straight.

  • Contrary to popular belief, the genes inherited from one’s parents do not set a child’s future development in stone.
    Variations in DNA sequences between individuals certainly influence the way in which genes are expressed and how the proteins encoded by those genes will function. But that is only part of the story—the environment in which one develops, before and soon after birth, provides powerful experiences that chemically modify certain genes which, in turn, define how much and when they are expressed. Thus, while genetic factors exert potent influences, environmental factors have the ability to alter the genes that were inherited.
  • Although frequently misunderstood, adverse fetal and early childhood experiences can—and do—lead to physical and chemical changes in the brain that can last a lifetime.
    Injurious experiences, such as malnutrition, exposure to chemical toxins or drugs, and toxic stress before birth or in early childhood are not “forgotten,” but rather are built into the architecture of the developing brain through the epigenome. The “biological memories” associated with these epigenetic changes can affect multiple organ systems and increase the risk not only for poor physical and mental health outcomes but also for impairments in future learning capacity and behavior.
  • Despite some marketing claims to the contrary, the ability of so-called enrichment programs to enhance otherwise healthy brain development is not known.
    While parents and policymakers might hope that playing Mozart recordings to newborns will produce epigenetic changes that enhance cognitive development, there is absolutely no scientific evidence that such exposure will shape the epigenome or enhance brain function. What research has shown is that specific epigenetic modifications do occur in brain cells as cognitive skills like learning and memory develop, and that repeated activation of brain circuits dedicated to learning and memory through interaction with the environment, such as reciprocal “serve and return” interaction with adults, facilitates these positive epigenetic modifications. We also know that sound maternal and fetal nutrition, combined with positive social-emotional support of children through their family and community environments, will reduce the likelihood of negative epigenetic modifications that increase the risk of later physical and mental health impairments.

The epigenome can be affected by positive experiences, such as supportive relationships and opportunities for learning, or negative influences, such as environmental toxins or stressful life circumstances, which leave a unique epigenetic “signature” on the genes. These signatures can be temporary or permanent and both types affect how easily the genes are switched on or off. Recent research demonstrates that there may be ways to reverse certain negative changes and restore healthy functioning, but that takes a lot more effort, may not be successful at changing all aspects of the signatures, and is costly. Thus, the very best strategy is to support responsive relationships and reduce stress to build strong brains from the beginning, helping children grow up to be healthy, productive members of society.

Considering interactions between genes, environments, biology, and social context

Kristen Jacobson received her Ph.D. in Human Development and Family Studies from the Pennsylvania State University in 1999. She spent a year as a postdoctoral scholar in psychiatric genetics under the direction of Dr. Kenneth Kendler at the Virginia Institute for Psychiatric and Behavioral Genetics, where she later served as faculty from 2000-2005. Dr. Jacobson is currently an Assistant Professor of Psychiatry at the University of Chicago, and serves as the Associate Director for Twin Projects and the Associate Director of the Clinical Neuroscience and Psychopharmacology Research Unit. Dr. Jacobson is a collaborator on a number of twin studies of children, adolescents, and adults, and is currently conducting a multidisciplinary, multi-level study of adolescent development, From Neighborhoods to Neurons and Beyond, funded by an NIH New Innovator Award . She is editor of a special issue of Behavior Genetics entitled Pathways between Genes, Brain, and Behavior (expected publication January, 2010). New areas of research involve pilot studies of epigenetics in both mice and humans.

Bronfenbrenner’s bioecological model (Bronfenbrenner & Ceci, 1994) highlights the need to consider interactions between individual, family, peer, school, and community characteristics in understanding individual differences in human development. In order to obtain a complete understanding of the processes involved in individual differences, multidisciplinary studies that measure risk and protective factors at multiple levels of analysis are required. With recent advances in human molecular genetics, the need to integrate environmental measures into genomic studies is of even greater importance. While the mapping of the human genome and the corresponding availability of genome-wide association analysis (GWAS) techniques has led to a flurry of research activity trying to discover “genes for” particular disorders and traits, a significant body of research, both historic as well as quite recent, cautions that efforts to uncover specific genetic variants that ignore the effects of social and contextual environments in genetic studies of individual differences in human behavior and traits may be futile. This essay briefly reviews some of the most interesting work regarding the interplay of genes and environments on individual differences in human development.

Nature versus Nurture

For years, behavioral genetic studies using twin or adoptive samples have been considered the gold standard for assessing the joint effects of nature and nurture in accounting for individual differences in human behaviors and traits. Decades of behavioral genetic research have demonstrated the importance of genetically-influenced characteristics on individual differences in child, adolescent, and adult behaviors and traits. At the same time, behavioral genetic studies have revealed that generally over half of the variation in individual behaviors and traits is due to environmental factors, typically environmental factors that are unique across people within the same family or that have different effects on behavior (i.e., nonshared environmental influence).

Genetic influence has been found on “environmental” measures, suggesting the presence of gene à environment correlations. Gene à environment correlations arise because exposure to certain risk and protective environments is not random, but rather is influenced by inherited characteristics of the individual, and also because children “inherit” both genes and environments from their parents. The role of genes and environments in mediating pathways between risk and behavior is complex, however. For example, recent quasi-longitudinal work using twins to understand the relationship between peer group deviance and adolescent problem behavior found that while genetic factors accounted for most of the relationship between earlier problem behavior and later peer group deviance (consistent with genetic characteristics of an individual relating to peer selection), the relationship between prior peer group deviance and later problem behavior was largely environmentally mediated (consistent with peer influence effects (Kendler, Jacobson, Myers, & Eaves, 2008).

Nature and Nurture

While the nature versus nurture debate may have attenuated in recent years with consensus from many fields regarding the importance of both genes and environments, other areas of research have further identified interactions between nature and nurture as important components of individual differences. A host of adoption studies in the 1980s and 1990s have shown that genetic liability to antisocial behavior (as indexed through biological parent psychopathology and substance abuse) is only associated with the development of adult criminality and aggression under adverse adoptive environmental conditions, indicating that neither nature nor nurture was sufficient in and of itself to cause pathology (Cadoret, Yates, Troughton, Woodworth, & Stewart, 1995 Cloninger & Gottesman, 1987).

Alternatively, gene X environment (gXe) interactions may be implicated when the relative importance of genetic influence on behaviors and traits as measured through standard twin designs varies across social and ecological context. For example, a study by Rowe, Almeida, and Jacobson (1999) integrated genetically-informative regression models within a hierarchical linear modeling design to show that levels of parental warmth, measured at the aggregate school level, moderated the heritability (i.e., proportion of individual differences due to genetic factors) of adolescent aggression. Heritabilities of delinquent behavior are increased among adolescents living in families with high rates of dysfunction (Button, Scourfield, Martin, Purcell, & McGuffin, 2005), while the heritability of adolescent smoking decreases with higher levels of parental monitoring (Dick et al., 2007). Family and personal religiosity has been shown to decrease the importance of genetic variance on adolescent substance use behaviors (Koopmans, Slutske, Heath, Neale, & Boomsma, 1999 Timberlake et al., 2006), and urban-rural differences in the heritability of adolescent alcohol use were found to be mediated by contextual factors such as alcohol sales and neighborhood migration (Dick, Rose, Viken, Kapiro, & Koskenvuo, 2001). These latter areas of research may be of particular importance in generalizing results from prior twin studies to minority individuals or individuals in socially and economically disadvantaged environments, as most large-scale twin registries are based on primarily middle-class, Caucasian or Asian samples.

More recently, attention has turned to using measured genotypes and measured environments to investigate ”classic” gXe interactions for a number of important behaviors. Caspi et al.(2002) have elucidated an important and highly replicated (Kim-Cohen et al., 2006) gXe interaction using measured genotype (MAO-A gene) and environmental risk (child abuse) variables, demonstrating that the relationship between child maltreatment and various indices of aggressive and antisocial behavior is attenuated among individuals with the high MAO-A activity genotype.

Another highly replicated interaction has been found between a serotonin transporter gene (5-HTTPLR) and stressful life events in predicting depression (Canli & Lesch, 2007). Further studies have found interactions between the 5-HTTPLR genotype and socioeconomic status (SES) for aggression in preadolescents (Nobile et al., 2007), between the 5-HTTPLR genotype and lab-induced stress for lab measures of aggression in adult males (Verona, Joiner, Johnson, & Bender, 2006) and between life stress and the 5-HTTPLR genotype for individual differences in amygdala activation (Canli et al., 2006). There is also emerging evidence for environmental modification of dopaminergic genes related to impulsivity and aggression, with studies finding significant interactions among the DRD4-7 repeat polymorphism and caregiver quality in predicting higher levels of aggression and impulsive traits in infants and preschoolers (Bakermans-Kranenburg & van Ijzendoorn, 2006 Sheese, Voelker, Rothbart, & Posner, 2007), and interactions between SES and the DRD4 gene for aggression in pre-adolescents (Nobile et al., 2007). Thus, genes implicated in multiple neurotransmitter pathways work in conjunction with a host of social and environmental experiences to alter individual differences across multiple behaviors and traits.

Additional Gene-Environment Interplay

While the above section concerns statistical interactions between genes and environments which may represent genetic sensitivity to environmental stressors, or, alternatively, environmental exacerbation of genetic effects, another potentially important avenue for research concerns the dynamic interplay between genes and environments, that is, genetic influence on environments and environmental influences on genes. By now, it is fairly common knowledge that when measures of family environment are treated as ‘phenotypes’ in traditional behavioral genetic models, significant genetic influences on these measures are often detected (Plomin & Bergeman, 1991). Decades of behavioral genetic studies have provided considerable evidence for significant genetic influence for measures such as various dimensions of parenting, indices of SES such as income and educational level, social support, and stressful life events (see Kendler & Baker [2007] for a recent review). What has been slower to develop, however, is the notion that environmental influences and experiences can have profound effects on genetic influence. While the underlying DNA structure and sequence individuals are born with does not change over time, a newer area of research in epigenetics is beginning to identify factors that may alter gene expression and function across the lifespan.

Epigenetics, defined formally as changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence, offers an exciting new frontier in the study of human psychiatric and medical diseases, and psychological behaviors and traits. Epigenetic mechanisms include DNA methylation and chromatin remodeling, the latter via post-translational modifications (e.g. methylation, acetylation, phosphorylation and ubiquitylation) to histone proteins which form the scaffold for the DNA helix. Although some epigenetic processes are essential to organism function (e.g., differentiation of cells in the developing embryo during morphogenesis), other epigenetic processes can have major adverse effects on health and behavioral outcomes. While some epigenetic changes only occur within the course of one individual organism's lifetime, animal models suggest that other epigenetic changes can be inherited from one generation to the next (see Champagne [2008] for a review), contributing, in part, to the heritability of behavioral traits and psychiatric disease.

However, a growing field of research suggests that environmental experiences, particularly those related to stress, have the capacity to alter biological and genetic mechanisms associated with increased risk of problem behavior. Again, the notion that environmental experience can change biological processes has important historical precedence. Harlow’s seminal deprivation studies of non-human primates have shown that disruptions in early rearing environments have the capacity to disrupt psychobiological regulatory functions, leading to behavioral changes. Other important animal research has begun to identify the precise mechanisms by which social environmental factors can alter epigenetic programming. Relatively recent research using animal models offers an elegant demonstration of how early environmental stressors can alter neurobiological responsivity to future stressful conditioning (Meaney, 2001). Meaney’s model highlights how individual differences in maternal behaviors can cause regulatory changes in the corticotropin releasing hormone (CRH) system at the level of the central nucleus of the amygdala, and how these changes relate further to changes in adrenocortical and autonomic effects of later stressful events. Importantly, his work suggests that these effects can be altered through intervention (Weaver et al., 2005). Differences in early maternal care have also been associated with differences in methylation of the glucocorticoid receptor gene promoter in the hippocampus (Meaney & Szyf, 2005). Most critically, a recent comparison of post-mortem brain tissue from a sample of patients with a history of child abuse and/or neglect and who died by suicide indicated DNA hypermethylation of the rRNA promoter region in the hippocampus relative to controls who experienced sudden, accidental death (McGowan et al., 2008), supporting the hypothesis that epigenetic changes due to social and environmental experiences are related to behavioral traits.

Other studies of monozygotic twins have identified variations in DNA methylation levels in certain target gene promoter regions. Because identical twins share identical genomes and experience many of the same family environmental factors, this indicates that environmental experiences that are not shared among children in the same family have an important causal role in gene expression, and may further be related to behavioral differences among identical twin pairs. Importantly, within-pair differences in DNA methylation and histone acetylation patterns were increased in older twin pairs, especially those who had different lifestyles and had spent fewer years of their lives together, strongly supporting epigenetic processes as a part of nonshared environmental influence on individual differences (Fraga et al., 2005). This suggests that epigenetic processes represent a fundamental gene-environment interface in the development and ongoing plasticity of the human brain.


While there is no doubt that genetic studies of individual behaviors and traits will increase our understanding of both normal human variation and pathological disorders, there is increasing recognition that the interplay between genes and environments is remarkably complex. Not only are both genes and environments important for both normal and abnormal human development, but genes and environments operate interactively to produce both risk and resilience to specific behavioral and psychiatric disorders. More importantly, emerging lines of research from epigenetics suggest that not only can nature alter nurture, but nurture, in turn, has the power to modify nature. Thus, genomic studies that incorporate a range of social and environmental influences will further our understanding of the complex dance between nature and nurture in human development.

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(This video is no longer available for streaming.) Once nurture seemed clearly distinct from nature. Now it appears that our diets and lifestyles can change the expression of our genes. How? By influencing a network of chemical switches within our cells collectively known as the epigenome. This new understanding may lead us to potent new medical therapies. Epigenetic cancer therapy, for one, already seems to be yielding promising results.


PBS air date: July 24, 2007

CHEERFUL NEIL DEGRASSE TYSON: Did you ever notice that if you get to know two identical twins, they might look alike, but they're always subtly different?


CHEERFUL NEIL DEGRASSE TYSON: As they get older, those differences can get more pronounced. Two people start out the same but their appearance and their health can diverge. For instance, you have more gray hair.

CANTANKEROUS NEIL DEGRASSE TYSON: No. No, I don't. Identical twins have the same DNA, exact same genes.


CANTANKEROUS NEIL DEGRASSE TYSON: And don't our genes make us who we are?

CHEERFUL NEIL DEGRASSE TYSON: Well they do, yes, but they're not the whole story. Some researchers have discovered a new bit of biology that can work with our genes or against them.

CANTANKEROUS NEIL DEGRASSE TYSON: Yeah, you're heavier, and I'm better looking.


NEIL DEGRASSE TYSON: Imagine coming into the world with a person so like yourself, that for a time you don't understand mirrors.

CONCEPCIí“N: As a child, when I looked in the mirror Iɽ say, "That's my sister." And my mother would say, "No, that's your reflection!"

NEIL DEGRASSE TYSON: And even if you resist this cookie-cutter existence, cultivate individual styles and abilities—like cutting your hair differently, or running faster—uncanny similarities bond you together: facial expressions, body language, the way you laugh—or dress for an interview, perhaps, when you hadn't a clue what your sister was going to wear. The synchrony in your lives constantly confronts you.

CLOTILDE: When I see my sister, I see myself. If she looks good, I think, "I look pretty today." But if she's not wearing makeup, I say, "My god, I look horrible!"

NEIL DEGRASSE TYSON: It's hardly surprising because you both come from the same egg. You have precisely the same genes. And you are literally clones, better known, as identical twins.

But now, imagine this: one day, your twin, your clone, is diagnosed with cancer. If you're the other twin, what can you do except wait for the symptoms?

CLOTILDE: I have been told that I am a high risk for cancer. Damocles' sword hangs over me.

NEIL DEGRASSE TYSON: And yet, it's not uncommon for a twin, like Ana Mari, to get a dread disease, while the other, like Clotilde, doesn't. But how can two people so alike, be so unalike?

Well, these mice may hold a clue. Their DNA is as identical as Ana Mari and Clotilde's despite the differences in their color and size. The human who studies them is Duke University's Randy Jirtle.

So, Randy, I see here you have skinny mice and fat mice. What have you done in this lab?

RANDY JIRTLE: Well, these animals are actually genetically identical.

NEIL DEGRASSE TYSON: The fat ones and the skinny ones?

RANDY JIRTLE: That's correct.

NEIL DEGRASSE TYSON: Because these are huge.

NEIL DEGRASSE TYSON: Can we weigh them and find out?

RANDY JIRTLE: Sure. So if you take this.

NEIL DEGRASSE TYSON: It looks like they can barely walk.

RANDY JIRTLE: They can't walk too much. They're not going to be running very far. So that's about 63 grams.


RANDY JIRTLE: Let's look at the other one.

NEIL DEGRASSE TYSON: So it's half the weight.

NEIL DEGRASSE TYSON: This gets even more mysterious when you realize that these identical mice both have a particular gene, called agouti, but in the yellow mouse it stays on all the time, causing obesity.

So what accounts for the thin mouse? Exercise? Atkins? No, a tiny chemical tag of carbon and hydrogen, called a methyl group, has affixed to the agouti gene, shutting it down. Living creatures possess millions of tags like these. Some, like methyl groups, attach to genes directly, inhibiting their function. Other types grab the proteins, called histones, around which genes coil, and tighten or loosen them to control gene expression. Distinct methylation and histone patterns exist in every cell, constituting a sort of second genome, the epigenome.

RANDY JIRTLE: Epigenetics literally translates into just meaning "above the genome." So if you would think, for example, of the genome as being like a computer, the hardware of a computer, the epigenome would be like the software that tells the computer when to work, how to work, and how much .

NEIL DEGRASSE TYSON: In fact, it's the epigenome that tells our cells what sort of cells they should be. Skin? Hair? Heart? You see, all these cells have the same genes. But their epigenomes silence the unneeded ones to make cells different from one another. Epigenetic instructions pass on as cells divide, but they're not necessarily permanent. Researchers think they can change, especially during critical periods like puberty or pregnancy.

Jirtle's mice reveal how the epigenome can be altered. To produce thin, brown mice instead of fat, yellow ones, he feeds pregnant mothers a diet rich in methyl groups to form the tags that can turn genes off.

RANDY JIRTLE: And I think you can see that we dramatically shifted the coat color and we get many, many more brown animals.

NEIL DEGRASSE TYSON: And that matters because your coat color is a tracer, is an indicator.

RANDY JIRTLE: That's correct.

NEIL DEGRASSE TYSON: . of the fact that you have turned off that gene?

NEIL DEGRASSE TYSON: This epigenetic fix was also inherited by the next generation of mice, regardless of what their mothers ate. And when an environmental toxin was added to the diet instead of nutrients, more yellow babies were born, doomed to grow fat and sick like their mothers.

It seems to me, this has profound implications for our health.

RANDY JIRTLE: It does, for human health. If there are genes like this in humans, basically, what you eat can affect your future generations. So you're not only what you eat, but potentially what your mother ate, and possibly even what your grandparents ate.

NEIL DEGRASSE TYSON: So how do you go to humans to do this experiment, when you have these mice, and they're genetically identical on purpose?

NEIL DEGRASSE TYSON: So, who is your perfect lab human?

RANDY JIRTLE: Well, then we look for identical humans, which are identical twins.


And that brings us to the reason why we're showing you Spanish twins. In 2005, they participated in a groundbreaking study in Madrid. Its aim? To show just how identical, epigenetically, they are or aren't.

MANEL ESTELLER (Spanish National Cancer Center): One of the questions of twins is, "If my twin has this disease, I will have the same disease?" And genetics tell us that there is a high risk of developing the same disease. But it's not really sure they are going to have it, because our genes are just part of the story. Something has to regulate these genes, and part of the explanation is epigenetics.

NEIL DEGRASSE TYSON: Esteller wanted to see if the twins' epigenomes might account for their differences. To find out, he and his team collected cells from 40 pairs of identical twins, age three to 74, then began the laborious process of dissolving the cells until all that was left were wispy strands of DNA, the master molecule that contains our genes.

Next, researchers amplified fragments of the DNA, until the genes themselves became detectable. Those that had been turned off epigenetically appear as dark pink bands on the gel. Now, notice what happens when the genes from a pair of twins are cut out and overlapped.

The results are far from subtle, especially when you compare the epigenomes of two sets of twins that differ in age. Here, on the left, is the overlapped DNA of six-year-old Javier and Carlos. The yellow indicates where their gene expression is identical.

On the right, is the DNA of 66-year-old Ana Mari and Clotilde. In contrast to the younger twins, hardly any yellow shines through. Their epigenomes have changed dramatically.

The study suggests that, as twins age, epigenetic differences accumulate, especially when their lifestyles differ.

MANEL ESTELLER: One of the main findings of our research is that epigenomes can change in function of what we eat, of what we smoke, of what we drink. And this is one of the key differences between epigenetics and genetics.

NEIL DEGRASSE TYSON: As the chemical tags that control our genes change, cells can become abnormal, triggering diseases like cancer. Take a disorder like MDS, cancer of the blood and bone marrow. It's not a diagnosis youɽ ever want to hear.

SANDRA SHELBY: When I went in, he started patting my hand, and he was going, "Your blood work does not look very good at all," and that I had MDS leukemia, and that there was not a cure for it. And, basically, I had six months to live.

NEIL DEGRASSE TYSON: Was epigenetics the reason? Could the silencing of critical genes turn normal cells into cancerous ones? It's scary to think that a few misplaced tags can kill you. But it's also good news, because we've traditionally viewed cancer as a disease stemming solely from broken genes. And it's a lot harder to fix damaged genes than to rearrange epigenetic tags. In fact, we already have a few drugs that will work. Recently, Sandra Shelby and Roy Cantwell participated in one of the first clinical trials using epigenetic therapy.

JEAN PIERRE ISSA (M.D. Anderson Cancer Center): The idea of epigenetic therapy is to stay away from killing the cell. Rather, what we are trying to do is diplomacy, trying to change the instructions of the cancer cells, reminding the cell, "Hey, you're a human cell. You shouldn't be behaving this way." And we try to do that by reactivating genes.

SANDRA SHELBY: The results have been incredible, and I didn't have really any horrible side effects.

ROY CANTWELL: I am in remission. And going in the plus direction is a whole lot better than the minus direction.

NEIL DEGRASSE TYSON: In fact, half the patients in the trial are now in remission. But, while it maybe easier to fix our epigenome than our genome, messing it up is easier, too.

RANDY JIRTLE: We've got to get people thinking more about what they do. They have a responsibility for their epigenome. Their genome they inherit. But their epigenome, they potentially can alter, and particularly that of their children. And that brings in responsibility, but it also brings in hope. You're not necessarily stuck with this. You can alter this.


NOVA scienceNOW

This material is based upon work supported by the National Science Foundation under Grant No. 0229297. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

The role of the repetitive genome

Transposable elements are intimate components of genomes, with gene regulatory potential that may lead to phenotypic diversity. Indeed, transposable elements and their relics constitute a major fraction of most eukaryotic genomes. McClintock proposed that transposons were turned on or off by environmental changes or during development, acting as ‘control elements’. We now know that transposons can influence gene activity in multiple ways, acting as regulatory elements or interfering with transcription 68 . Genomes have evolved species-specific mechanisms to limit transposon activity, for example by targeting repressive heterochromatin machinery, either through specific RNAs or DNA binding factors. In Drosophila, heterochromatin-dependent mechanisms allow the expression of specific clusters of transposon relics in order to produce PIWI-interacting RNAs (piRNAs) that, in turn, inhibit transposition. piRNAs are maternally heritable and can be amplified via a ping-pong system, effectively allowing the organism to resist new invasions and adapt their genome to them 69 . Caenorhabditis elegans uses heterochromatin components to prevent illegitimate repetitive DNA transcription and genome instability 70 . Plants produce small RNAs derived from double-stranded precursors, which are synthesized by dedicated polymerases and target DNA methylation and the H3K9 methylation machinery 71 . Finally, numerous strategies are deployed in mammals, the most recently characterized being the repression of endogenous retroviruses (ERVs) by the KAP1 protein (also known as TRIM28), which co-recruits heterochromatin proteins such as SETDB1 by interacting with Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs). This strategy also enables the rapid evolution of gene regulation strategies via binding of KZFP to ERVs near genes 72 , thus influencing gene expression dynamics and levels.

Learning and remembering

The basis of all behavior is learning and memory. Epigenetic modifications to a number of genes have now been shown to figure in learning and remembering.

J. David Sweatt, director of the McKnight Brain Institute at the University of Alabama at Birmingham, notes a striking parallel between developmental processes and the mechanisms of memory—changes driven by experience—in the adult nervous system. “It's not just that development and behavioral memory are rough analogs of each other, but rather that they are molecular homologues of each other,” he says. The two most studied epigenetic processes—regulation of the structure of three-dimensional DNA and its associated proteins, plus chemical adjustments to DNA through mechanisms like histone modification—are essential both in development and in long-term memory formation. “It's as if evolution has been efficient in the set of molecular mechanisms that cells use to trigger persisting changes. It uses those mechanisms in development when it's patterning the organism, when it's turning an embryonic stem cell into a neuron or a liver cell,” he says. “Then in the adult nervous system it has coopted some of those same mechanisms to trigger experience-dependent, persisting change in the function of neurons in the nervous system.”

Several studies have established that both DNA methylation and histone modifications are essential for learning and remembering. Some examples are based on fear conditioning, in which mice learn to show fear of a particular location where they have been subjected to electric shocks. After this conditioning, DNA methyltransferase, the enzyme that attaches a methyl group to DNA, increases in the hippocampus, the brain region where memories are forged. Inhibiting the enzyme prevents memories from forming. Forming memories of and remembering this contextual fear also boosts acetylation of histones in the hippocampus. Blocking histone acetylation therefore interferes with the behavior usually associated with the fear, but blocking deacetylation reverses these effects and also strengthens the formation of the fear memories.

Epigenetics may function in important ways during early development and in response to a variety of environmental triggers. Some of the mechanisms thought to be involved are DNA methylation, DNA packaging by histones, and histone modifications. Illustration: National Institutes of Health.

Epigenetics may function in important ways during early development and in response to a variety of environmental triggers. Some of the mechanisms thought to be involved are DNA methylation, DNA packaging by histones, and histone modifications. Illustration: National Institutes of Health.

It used to be—and still is, to some extent—that researchers believed that once epigenetic marks—particularly DNA methylation—were made, they were immutable except in special cases like cancer. The central dogma dictated that that the marks were laid down when cell fate was determined, and that those marks were unchangeable for the remainder of an animal's lifetime.

Now the take-home message from Sweatt's lab and those of other behavioral epigenetics pioneers of the mammal nervous system, such as Michael Meaney of Douglas Hospital and Moshe Szyf of McGill, both in Montreal, and Eric Nestler at Mount Sinai in New York City, is just the opposite. Recent work from labs investigating this new subfield of behavioral epigenetics has shown, Sweatt says, that there is dynamic regulation of epigenetic marks in nondividing cells in the mature nervous system. At least a subset of genes undergo active demethylation and remethylation, which is driven by the environment or by experience. This dynamism, he says, can lead to either transient or persistent functional changes in the nervous system.

Sweatt's recent work has concerned the potential role of DNA methylation in regulating long-term memory storage in the cortex. He and his colleagues have reported that putting DNA methytransferase inhibitors into an animal's anterior cingulate cortex a month after it has learned something partly erases that memory, diminishing it by half. The role of DNA methylation in long-term memory storage is at the moment a wide-open question and a focus in his lab, Sweatt says.


Chromatin structure defines the state in which genetic information in the form of DNA is organized within a cell. This organization of the genome into a precise compact structure greatly influences the abilities of genes to be activated or silenced. Epigenetics, originally defined by C.H.Waddington (1) as ‘the causal interactions between genes and their products, which bring the phenotype into being’, involves understanding chromatin structure and its impact on gene function. Waddington's definition initially referred to the role of epigenetics in embryonic development however, the definition of epigenetics has evolved over time as it is implicated in a wide variety of biological processes. The current definition of epigenetics is ‘the study of heritable changes in gene expression that occur independent of changes in the primary DNA sequence’. Most of these heritable changes are established during differentiation and are stably maintained through multiple cycles of cell division, enabling cells to have distinct identities while containing the same genetic information. This heritability of gene expression patterns is mediated by epigenetic modifications, which include methylation of cytosine bases in DNA, posttranslational modifications of histone proteins as well as the positioning of nucleosomes along the DNA. The complement of these modifications, collectively referred to as the epigenome, provides a mechanism for cellular diversity by regulating what genetic information can be accessed by cellular machinery. Failure of the proper maintenance of heritable epigenetic marks can result in inappropriate activation or inhibition of various signaling pathways and lead to disease states such as cancer (2,3).

Recent advances in the field of epigenetics have shown that human cancer cells harbor global epigenetic abnormalities, in addition to numerous genetic alterations (3,4). These genetic and epigenetic alterations interact at all stages of cancer development, working together to promote cancer progression (5). The genetic origin of cancer is widely accepted however, recent studies suggest that epigenetic alterations may be the key initiating events in some forms of cancer (6). These findings have led to a global initiative to understand the role of epigenetics in the initiation and propagation of cancer (7). The fact that epigenetic aberrations, unlike genetic mutations, are potentially reversible and can be restored to their normal state by epigenetic therapy makes such initiatives promising and therapeutically relevant (8).

In this review, we take a comprehensive look at the current understanding of the epigenetic mechanisms at work in normal mammalian cells and their comparative aberrations that occur during carcinogenesis. We also discuss the idea of cancer stem cells as the originators of cancer and the prospect of epigenetic therapy in designing efficient strategies for cancer treatment.

Genetic mosaicism: does epigenetics have anything to do with it?

Recently, I was reading about the phenomenon of genetic mosaicism and its implications for the development of human diseases. Generation of genetically distinct cells from a single zygote is caused by de novo mutational events, including large chromosomal alterations (whole-chromosome aneuploidy, segmental aneuploidy). In addition, advances in sequencing-based approaches demonstrated how mosaicism could as well arise following subtler rearrangements and substitutions at the level of a single nucleotide (Lupski 2013). By altering the cell’s transcriptional programme, these genetic aberrations can predispose cancer development, but are also found in numerous non-cancer diseases, notably dermatological diseases, where mosaicism is directly reflected in the patients’ phenotypic variation (Biesecker and Spinner 2013). However, one should not forget the existence of epigenetic modifications that superimpose the information written in our genes and thus modulate how this information is read. And these modifications come in numerous flavours, known for a long time to differentiate different cell types in an organism. Therefore, I believe the only true insight into phenotypic and physiological consequences of mosaicims requires studying both aspects simultaneously.

One wonders, how (if at all) does an “altered” cell deal with a chromosomal rearrangement? Can it recruit epigenetic means to somehow put the genetic alteration under control or attenuate its impact and arousal of unscheduled changes leading to disease? I was happy to come across a study where the authors show how trisomy 8-positive fibroblasts display a characteristic expression and methylation phenotype distinct from disomic fibroblasts from the same patient (Davidsson 2013). But, regardless of the reported massive changes, increased DNA hypomethylation of gene-poor regions on the gained chromosome – potentially as part of the heterochromatinization process reminiscent of inactivated X-chromosome in females – might argue in favor of a defense mechanism activated to restrain the unfavorable state. So, it made me wonder whether using drugs that target epigenetic modifications (histone deacetylase and DNA methylation inhibitors) or modern gene manipulation tools targeting a specific gene, region and even potentially a nucleotide (e.g. TALENs) could aid preventing the negative impacts of genetic rearrangements. Of course, the drug specificity and the magnitude of a chromosomal rearrangement still seem to be the limiting factors. Targeting only the affected cells poses an additional layer of complexity.

But, there is one other mosaicism-related issue that preoccupies my mind. Is there such a phenomenon as “epigenetic mosaicism”? Interestingly, searching Google does not take me far… This type of mosaicism would constitute an imaginary scenario wherein two genetically identical cells of the same cell type have different expression profiles, solely due to different epigenetic profiles. We know epigenetic alterations are equally important in cancer development, but can they be a sole driver of phenotypic variability in between cells of the same type, leading to mosaicism or disease/cancer? Or, rather, are genetic changes the ones that preferentially mess things up, followed further by epigenetic alterations that help to maintain and/or propagate an unfavourable condition?

When observing various tissue sections under the microscope, cells of the same type can assume various positions in regard to the blood supply and local microenvironment (other cell types). Therefore, it seems legitimate to think they might be physiologically “slightly” different, with “slightly” different expression profiles defined by “slightly” different epigenetic patterns. Would this constitute mosaicism as well – phenotypically harder to observe and with no, or, in the worst case scenario, less pronounced consequences on human health? More importantly, do we need to redefine the number of cell types that inhabit our body, taking into account epigenetic profiles that even in morphologically and physiologically identical cells might differ? What benefits would this new “cell systematics” bring, understanding that what was until recently considered a homogenous cell population, would suddenly become a highly diverse population of cells. Do we even have technical and methodological means to study this properly?

Still, none of this should be taken too seriously… these are just thoughts of an ordinary postdoc who still has a lot to learn…