Stem Cells Memories – Erasing Them Might Unlock the Doorway to Enhanced Treatments

Special types of cells called stem cells exist in our bodies and can differentiate into any other form of cell. Stem cell research is currently being conducted to repair damaged cells in disorders like Parkinson’s. They have enormous potential for therapy.

Human embryos can be used as a source of stem cells, but this has both ethical and practical drawbacks. Another method is to create “induced pluripotent stem cells” (iPS cells) using adult skin or other tissue cells.

When we try to change these cells into other sorts of cells, they occasionally retain a “memory” of the type of cell they previously were, which can make them less predictable or effective.

In order to make iPS cells behave more like embryonic stem cells, we have discovered a mechanism to remove this memory. Our research was featured in Nature.

Boundless Potential within the Realm of Regenerative Medicine

In the lab, skin cells and other mature, specialized cells can be reprogrammed to become iPS cells. Regenerative medicine, which aims to create, fix, or replace diseased or damaged cells, organs, or tissues, holds immense potential for these “blank slate” cells.

There is less chance that the new cells will be rejected by the patient’s immune system because scientists can create iPS cells from the patient’s own tissue.

One instance is the testing of iPS cells to create insulin-producing pancreas cells to aid diabetics. Although we’re not there yet, it serves as a conceivable scenario.

While the field of iPS cell research is developing quickly, there are still many technical obstacles to overcome. Researchers are still working to improve their ability to regulate the cell types that iPS cells develop into and guarantee the process is secure.

The “epigenetic memory” of iPS cells, where they retain vestiges of the cell type they were previously, is one of these technical difficulties.

Epigenetic Memory: A Hitch in iPS Cell Utility

Let’s first discuss epigenetics in order to comprehend “epigenetic memory”. Genes are sets of instructions found in our DNA. Epigenetics, which means “above genetics,” is the study of how numerous stimuli can affect gene function (turning it on or off) without altering the DNA sequence itself.

The term “epigenome” refers to all of a cell’s epigenetic changes as a whole. The DNA in each of our cells is identical, but the epigenome regulates which genes are activated or inactive, determining whether a cell develops into a heart cell, kidney cell, liver cell, or any other form of cell.

The epigenome can be compared to a set of bookmarks, and the DNA to a cookbook. The recipes are not changed by the bookmarks; rather, they specify which ones to utilize.

Similar to genetic markers, epigenetic markers help cells comprehend genetic code without altering it.

We aim to remove all of a mature cell’s “bookmarks” when we reprogram it to become an iPS cell. This doesn’t always work perfectly though. This “epigenetic memory” can affect the behavior of the iPS cells when certain bookmarks are still present.

An iPS cell derived from a skin cell may retain some “memory” of its former self, increasing the likelihood that it will revert to being a skin-like cell and decreasing the likelihood that it will differentiate into another type of cell. This is so because some epigenetic markers on the DNA can instruct a cell to act like a skin cell.

Because it can affect the process of converting iPS cells into the desired cell types, this can be a barrier to employing iPS cells. It might also have an impact on how the cells work after they have been formed. If you want to employ iPS cells to rebuild a pancreas, but the cells retain the “memory” of being skin cells, the iPS cells may not perform as effectively as real pancreatic cells.

Unshackling iPS Cell Epigenetic Memory to Elevate Their Performance

It is commonly acknowledged that one of the challenges facing regenerative medicine is overcoming the problem of epigenetic memory in iPS cells.

Studying how the epigenome changes when adult skin cells are converted into iPS cells allowed us to develop a new method of cell-reprogramming that more thoroughly removes epigenetic memories. We made this discovery by reprogramming cells in a manner that mimics the natural reset of the epigenome in embryonic cells.

The epigenetic imprints inherited from the sperm and egg cells are essentially erased during the early stages of an embryo’s development, before it is placed into the uterus. Early embryonic cells can now start over and differentiate into any cell type as the embryo grows and develops thanks to this reset.

We produced iPS cells that are more similar to embryonic stem cells than regular iPS cells by including a phase during the reprogramming process that momentarily replicates this reset process.

The medicinal potential of iPS cells will increase with more successful epigenetic memory erasure. The iPS cells will be able to act as “blank slates” similar to embryonic stem cells, increasing the likelihood that they will differentiate into any chosen cell type.

IPS cells can more reliably transform into any type of cell and aid in the creation of certain cells required for therapies, such as new insulin-producing cells for people with diabetes or brain cells for people with Parkinson’s, if they have the ability to forget their previous identities. Using iPS cells in medical therapies may also lower the likelihood of unforeseen behaviors or consequences.

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