Molecular players in cellular reprogramming – a review

by Alexey Bersenev on October 2, 2012 · 0 comments

in notes, reviews

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Molecualar Cell journal features a review by Thomas Vierbuchen and Marius WernigMolecular Roadblocks for Cellular Reprogramming. If you’re interested in iPS cells, reprogramming and transdifferentiation, you can’t miss it!

The authors overview the history and major milestones in cellular reprogramming. Interestingly, they argue that mature cells, probably can not be reversed completely to “ground zero”, because of “epigenetic memory”:

“Epigenetic memory” refers to remnants of transcriptional properties or chromatin features typical of the starting cell type after reprogramming. The persistence of epigenetic memory is a critical issue in the reprogramming field because it has the potential to modify the behavior of reprogrammed cells, which could have large consequences for in vitro disease modeling studies and any future clinical applications of reprogrammed cells.

More on hypothesis of “active conversion versus return”:

… reprogramming between distantly related somatic lineages is possible without passing through the pluripotent state and suggested that reprogramming fibroblasts into pluripotent stem cells might represent an active conversion process rather than a return to the default cellular state following erasure of chromatin marks associated with cellular specification.

While ago we even didn’t think about such important role of epigenetics in lineage fidelity. Now, we know that epigenetic memory persists in any reprogramming process. For example, so-called iN (induced neuronal) cells directly reprogrammed from hepatocytes, retain some genetic and epigenetic marks of original cells (hepatocytes) at single cell level.

Further work will be required to determine the extent to which epigenetic memory affects the functional properties of reprogrammed cells. It will also be interesting to determine the molecular basis of epigenetic memory, whether different reprogramming methods lead to more or less epigenetic memory, and whether certain loci are more resistant to complete reprogramming than others, as has been seen during reprogramming to pluripotency under certain experimental conditions.

Highly recommended to read!

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