Epigenetics Controls stem cells not Darwin


Article Mesenchymal Stem Cells Under Epigenetic Control – The Role of Epigenetic Machinery in Fate Decision and Functional Properties

Mesenchymal stem cells (MSCs) are a type of adult stem cell that can differentiate into a variety of different cell types, including bone, fat, and cartilage. MSCs have the potential to be used in a variety of regenerative medicine applications, but their differentiation and function are tightly regulated by epigenetic mechanisms. Epigenetic modifications are changes to the DNA or its associated proteins that do not alter the underlying DNA sequence as per neo darwinism. These modifications can have a profound impact on gene expression and cellular function.

This article discusses the role of epigenetic machinery in MSC fate decision and functional properties. They begin by providing a brief overview of epigenetic modifications and their mechanisms of action. They then discuss the specific epigenetic changes that occur during MSC differentiation and how these changes are regulated by epigenetic modifiers. Finally, they discuss the potential therapeutic implications of manipulating epigenetic machinery to control MSC fate and function.

Epigenetic modifications are reversible changes to the DNA or its associated proteins that do not alter the underlying DNA sequence. These modifications can have a profound impact on gene expression and cellular function. Epigenetic modifications are essential for normal development and cell differentiation, and they also play a role in a variety of diseases, including cancer.

There are three main types of epigenetic modifications: DNA methylation, histone modifications, and non-coding RNAs.

  • DNA methylation is the addition of a methyl group to the DNA molecule. DNA methylation can repress gene expression by preventing transcription factors from binding to DNA.

  • Histone modifications are changes to the histone proteins that DNA is wrapped around. Histone modifications can either open or close up the DNA, which affects gene expression.

  • Non-coding RNAs are RNA molecules that do not code for proteins. Non-coding RNAs can regulate gene expression by interacting with DNA, RNA, or proteins.

MSCs are multipotent stem cells that can differentiate into a variety of different cell types, including bone, fat, and cartilage. The fate of an MSC is determined by a combination of genetic and environmental factors. Epigenetic modifications play a key role in regulating the response of MSCs to environmental cues and, therefore, in determining their fate.

A number of different epigenetic modifiers have been shown to play a role in MSC differentiation. For example, the histone deacetylase HDAC1 is essential for adipocyte differentiation. HDAC1 represses the expression of genes that promote osteogenesis and chondrogenesis, while activating the expression of genes that promote adipogenesis.

Another important epigenetic modifier in MSC differentiation is the DNA methyltransferase DNMT1. DNMT1 is responsible for maintaining DNA methylation patterns. DNMT1 activity is required for MSC differentiation into osteoblasts and chondrocytes, but it inhibits adipocyte differentiation.

In addition to regulating fate decision, epigenetic modifications also regulate the functional properties of MSCs. For example, the expression of immunomodulatory genes in MSCs is regulated by epigenetic modifications. MSCs can suppress the immune system and promote tissue repair. This is due in part to the expression of immunomodulatory genes, such as IL-10 and TGF-β. The expression of these genes is regulated by epigenetic modifications, such as histone acetylation and DNA demethylation.

The ability of epigenetic modifications to control MSC fate and function has important implications for regenerative medicine. By manipulating epigenetic machinery, it is possible to control the differentiation and function of MSCs, which could lead to new and improved treatments for a variety of diseases.

For example, epigenetic modifiers have been shown to promote the differentiation of MSCs into osteoblasts, chondrocytes, and other cell types that are important for tissue repair. This suggests that epigenetic modifiers could be used to enhance the efficacy of MSC-based therapies for a variety of diseases, such as osteoporosis and osteoarthritis.

In addition, epigenetic modifiers could be used to modulate the immunomodulatory properties of MSCs. This could lead to new and improved treatments for autoimmune diseases and inflammatory disorders.

Epigenetic modifications play a key role in regulating MSC fate decision and functional properties. By understanding how epigenetic machinery controls MSCs, it is possible to develop new and improved treatments for a variety of diseases.

The conclusions of the article challenges neo darwinism by demonstrating that the environment can have a significant impact on gene expression and cellular differentiation without altering the underlying DNA sequence.

Neo Darwinism is a theory of evolution that is based on the principles of natural selection and random variation (mutations). One of the key tenets of neo darwinism is that evolution is gradual and irreversible. This is because changes in DNA sequence are required for new traits to arise. However, the article cited above shows that epigenetic modifications can lead to changes in gene expression and cellular differentiation without altering the underlying DNA sequence. This suggests that evolution can occur more rapidly and reversibly than previously thought.

Another challenge that epigenetic regulation poses to neo darwinism is that it can lead to the inheritance of acquired traits. This is because epigenetic modifications can be passed down from generation to generation. For example, a study published in the journal Nature Neuroscience in 2014 showed that exposure to stress during pregnancy can lead to epigenetic changes in the offspring that result in increased anxiety and depression later in life.

These findings suggest that epigenetic regulation can play a significant role in evolution, even though it does not involve changes in DNA sequence. This challenges the traditional neo darwinian view that evolution is due to changes in the DNA due to random mutations. Epigenetics controls gene expression without mutations.

Here are some specific examples of how epigenetic regulation challenges neo darwinism:

  • Epigenetic regulation can lead to rapid changes in gene expression. For example exposure to a particular type of bacteria can cause epigenetic changes in fruit flies that lead to a change in their immune response within a single generation.

  • Epigenetic regulation can lead to reversible changes in gene expression.  Epigenetic changes can cause the reversible silencing of genes that are involved in the development of cancer.

  • Epigenetic changes can be inherited. For example studies show that epigenetic changes associated with obesity can be inherited by offspring, even if the offspring are not themselves obese.

These findings suggest that epigenetic regulation plays a significant role in evolution, and that it can lead to rapid, reversible, and heritable changes in gene expression. This challenges the traditional neo darwinian view that evolution is gradual, irreversible, and driven solely by changes in DNA sequence.


References:

Epigenetic regulation of mesenchymal stem cell aging through histone modifications

https://doi.org/10.1016/j.gendis.2022.10.030


Epigenetic control of mesenchymal stem cells orchestrates bone regeneration

https://www.frontiersin.org/articles/10.3389/fendo.2023.1126787/full


Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

https://www.hindawi.com/journals/sci/2011/201371/

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