Wiping The Slate Clean: Epigenetic Eraser Can Revert Cells Back To A Pluripotent State

Resetting the epigenetic controls regulating your DNA can trigger creation of pluripotent cells with abilities mirroring embryonic stem cells

We can already create pluripotent cells by introducing particular protein factors that instruct cells to revert back to a flexible state in which they can form multiple cell types. They’re not completely identical to embryonic stem cells yet however, and many researchers are working on improving them even further to ensure they don’t retain the marks of an older cell. 

One area important to stem cell field is epigenetics. Epigenetic elements regulate your DNA, turning specific genes off or on. When embryonic stem cells are formed in the developing embryo, they undergo an epigenetic ‘wipe’ which removes most of their previous instructions. This means each new person begins again with a (mostly) clean slate, although there is evidence some marks can linger on, caused by extreme trauma for example. .

A new method of stem cell creation?

Researchers have now demonstrated that by applying a drug which acts like an epigenetic ‘eraser’ on mouse epiblast stem cells can revert them back to a pluripotent, embryonic state. Epiblast stem cells are a step further than embryonic types, having already began on the differentiation road into specific tissue. 

Induced pluripotent stem cells were a huge breakthrough, but can we do better?

“We’ve demonstrated that we don’t have to manipulate the pluripotent genes to get to the ground state, but rather that we can block all other options of where the cell ‘wants’ to go. Then the only option is going back to the ground, or naïve, pluripotent state”

The compound in use, MM-401, was originally designed for use in leukaemia but after a few days application to these cells it was able to induce pluripotency. We can already do this to an extent, but it could be that this new method actually works better – removing resistant, pesky epigenetic marks.

Blocking silencing

One particular gene called MLL1 is used by your cells to attach silencing methyl groups to your packaged DNA, and this plays an important role in differentiating adult cells. The MM-401 drug works by interfering with this process and blocking MLL1, forcing the cell into a less controlled state. Placing a roadblock on differentiation appears to trigger pluripotency as a default response, at least in mouse cells anyway.  

“People have been focused on other epigenetic changes that are more dramatic, but ignored methylation by the MLL family. Deleting MLL1 entirely causes failure later in differentiation, but inhibiting it with a drug temporarily leaves no trace behind”

Read more at Phys.org