Epigenetics At A Glance
Epigenetics Role in Stem Cells
Stem cells have a very important job within our bodies. They divide to replenish and repair cells without limit, acting as an internal repair system within our body, as long as the organism is alive. They can remain dormant for years and only act when they need to, such as when the cells they are responsible for replacing are diseased, dead or damaged. When a stem cell divides, each new cell has the potential either to remain a stem cell or become a cell with a more specialized function, such a red blood cell or a brain cell. Under physiologic or experimental conditions, stem cells can become tissue or organ specific cells. For example, in bone marrow, stem cells divide to repair and replace the damaged/worn tissue.Their ability to develop into many different cell types has caused a revolution in the future of medicine and has allowed scientists to gain more knowledge about human and disease development.
It's critical to understand epigenetic changes in reprogrammed cells, which can help detect whether the epigenetics of the cell look more like the original cell or the desired reprogammed cell. Reprogramming stem cells isn't always successful because there's a chance they could retain cellular memory of their original tissue, which is why epigenetics plays such a key role in understanding stem cells. Understanding the behavior of a cell will advance the development of successful stem cell therapies (24). Epigenetics could also potentially assist in overcoming development and differentiation challenges of stem cells through methylation. Methylation alters gene expressions and also acts as a sort of cellular memory for the cells, allowing cells to not only gain but preserve their differentation which gives them their different specialized functions (40). Without epigenetics and the understanding of epigenetics, stem cell therapies could be incredibly risky if they cannot maintain their reprogramming permanently.
UCLA School of Dentistry Professor and leading cancer scientist Dr. Cun-Yu Wang and his research team discovered two key epigenetic regulating genes that control the cell-fate determination of human bone marrow stem cells. They found two gene-activating enzyms, KDM4B and KDM6B, were capable of promoting stem cells' differentiation into bone cells by removing methyl markers from histone proteins. This process happens when the activation of certain genes favor a commitment to one lineage while the deactivation of genes favors other lineages at the same time.
Dr. Cun-Yu Wang and his team's profound research signify that chemical manipulation of these gene-activating enzymes may allow stem cells to differentiate specifically into bone cells, while inhibiting their differentiation into fat cells. The group's research could pave the way toward identifying potential therapeutic targets for stem cell–mediated regenerative medicine, as well as the treatment of bone disorders. (28)
Breakthroughs in Cellular Reprogramming through Epigenetics
The IRM Program in Cellular Reprogramming and Epigenetics consists of researchers from Penn’s Schools of Medicine, Veterinary Medicine, and Engineering and Applied Science.
This program's main focus is to investigate the means by which cells in embryonic development and tissue regeneration gain specialized functions and how a cell of one function can be converted to another. The program hopes to understand these principles so they can generate new cells and tissues for treating a wide variety of human injuries and disease. (27)
Discoveries Made by the IRM Program:
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Cell culture conditions where stem cells could be programmed to make functional insulin-producing cells were discovered. (27)
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Chromosomal modifications in early embryonic cells that can predict the ability of the cells to make liver or pancreas tissue were discovered. This information has lead to attempts to program stem cells for liver diseases and diabetes. (27)
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IRM researchers tested subunits of chromosomal proteins for novel functions in reproductive cells in fungi and discovered important protein modifications that are conserved in function in mammalian sperm. These studies integrate with IRM research on human fertility and reproduction. (27)
