Erasing Epigenetic Memory of iPS Cells to Make Them as Functional as Embryonic Stem Cells

Tuesday - August 22 2023, 11:29 UTC - 1 year ago

Stem cells have huge potential for medicine, and trials are currently under way using stem cells to replace damaged cells in diseases like Parkinson’s. One way to get stem cells is from human embryos, but this has ethical concerns and practical limitations. Another way is to turn adult cells from the skin or elsewhere into induced pluripotent stem cells (iPS cells). However, these cells sometimes carry a 'memory' of the kind of cell they used to be, which can make them less predictable or efficient. In a study published in Nature, the author and colleagues have found a way to erase this memory, making iPS cells as functional as embryonic stem cells.

Stem cells are special kinds of cells in our bodies that can become any other type of cell. They have huge potential for medicine, and trials are currently under way using stem cells to replace damaged cells in diseases like Parkinson’s.

One way to get stem cells is from human embryos, but this has ethical concerns and practical limitations. Another way is to turn adult cells from the skin or elsewhere into what are called "induced pluripotent stem cells" (iPS cells).

However, these cells sometimes carry a "memory" of the kind of cell they used to be, which can make them less predictable or efficient when we try to turn them into other types of cells.

In a study published in Nature, my colleagues and I have found a way to erase this memory, to make iPS cells function more like embryonic stem cells.

Great Promise for Regenerative Medicine .

Mature, specialized cells like skin cells can be reprogrammed into iPS cells in the lab. These "blank slate" cells show great promise in regenerative medicine, a field focused on regrowing, repairing, or replacing damaged or diseased cells, organs, or tissues.

Scientists can make iPS cells from a patient’s own tissue, so there’s less risk the new cells will be rejected by the patient’s immune system.

To take one example, iPS cells are being tested for making insulin-producing pancreas cells to help people with diabetes. We’re not there yet, but it’s an example of what might be possible.

Research using iPS cells is a rapidly advancing field, yet many technical challenges remain. Scientists are still figuring out how to better control what cell types iPS cells become and ensure the process is safe.

One of these technical challenges is overcoming "epigenetic memory," where the iPS cells retain traces of the cell type they once were.

Epigenetic Memory and How It Can Impair the Use of iPS Cells .

To understand "epigenetic memory," let’s first talk about epigenetics. Our DNA carries sequences of instructions known as genes. When various factors influence gene activity (turning them on or off) without changing the DNA sequence itself, this is known as epigenetics—literally meaning "above genetics." .

A cell’s epigenome is a collective term to describe all the epigenetic modifications in a cell. Each of our cells contains the same DNA, but the epigenome controls which genes are turned on or off, and this determines whether it becomes a heart cell, a kidney cell, a liver cell, or any other cell type.

You can think of DNA as a cookbook and the epigenome as a set of bookmarks. The bookmarks don’t alter the recipes, but they direct which ones are used.

Similarly, epigenetic marks guide cells to interpret the genetic code without changing it.

When we reprogram a mature cell into an iPS cell, we want to erase all its "bookmarks." However, this doesn’t always work completely. When some bookmarks remain, this "epigenetic memory" can influence the behavior of the iPS cells.

An iPS cell made from a skin cell can retain a partial "memory" of being a skin cell, which makes it more likely to turn back into a skin-like cell and less likely to turn into other cell types. This is because some of the epigenetic marks remain the same as what they were when the cell was still a skin cell.