Epigenetic Memory Erasure in Stem Cells May Be the Key to Better Regenerative Therapies

Stem cells have the unique ability to develop into specialized cell types in the human body. They are utilized for their great potential in medicine, especially in treatments that need repair or replacement of damaged or diseased cells.

These cells can be obtained from human embryos, but this method has ethical issues and practical limitations. Another approach is to get adult cells from the skin or any body part and turn them into induced pluripotent stem cells (iPS cells). However, these cells may carry a "memory" of the type of cell they used to be, making them less efficient when converted into other types of cells.

Effects of Stem Cell Memory

DNA molecules are composed of segments that carry genetic information known as genes. When various factors influence gene activities without changing the DNA sequence, this is known as epigenetics which means "above genetics."

Every individual cell contains the same DNA, but the epigenome or the epigenetic modification determines which genes are turned on or off. It also controls what kind of specialized cells the stem cells will become.

When a mature cell is reprogrammed into an iPS cell, experts aim to erase all its memories, but it does not always work ultimately. As a result, every remaining epigenetic memory can influence the behavior of the iPS cells.

For instance, an iPS cell obtained from a skin cell can keep a partial memory of being a former skin cell. It tends to return - like cells and is less likely to turn into other specialized cell types. This is because some of the epigenetic marks in the DNA can instruct the cell to behave like a skin cell.

This poses a challenge in using iPS cells because it can affect the process of converting iPS cells into the target type of cell. Furthermore, it can also influence the function of the cells once they are created.

Erasing the Epigenetic Memory

Overcoming the challenges posed by epigenetic memory in iPS cells is a huge concern in regenerative medicine. In response, a team of Australian researchers developed a new method of reprogramming human cells to mimic embryonic stem cells better. Led by Professor Jose M. Polo from Monash University, they created the transient-naïve-treatment (TNT) reprogramming, which simulates the cell's epigenome that occurs at the very early stage of embryonic development.

By studying the way somatic cells' epigenomes transform throughout the reprogramming process, they were able to spot the emergence of epigenetic anomalies. This way, they successfully introduced a new step of resetting epigenome to prevent these aberrations and wipe out the memory.

Before the embryo is implanted into the uterus during its early stage of development, the inherited epigenetic marks from the sperm and egg cells are erased. This allows the early embryo cell to start anew and become any cell as it grows and develops. Introducing a step during the reprogramming process mimicking this reset stage makes iPS cells more like embryonic stem cells than conventional iPS cells.

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