Molecular Medicine Israel

An Alternative Splicing Switches Embryonic Stem Cell Pluripotency & Reprogramming

Cell, Volume 147, Issue 1, 132-146, 15 September 201

Alternative splicing  of a gene called FOXP1, is switching between active expression in embryonic stem cells and silent status in “adult” cells.  It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency,” said Prof. Benjamin Blencowe, The principal investigator on the study . “We’re beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications.” The findings were published in the current online edition of the scientific journal Cell.

The splicing event discovered by Blencowe’s team, changes the DNA binding properties of FOXP1 in a way that then controls the expression of the core pluripotency transcription factors, to facilitate maintenance of pluripotency. “As a mechanism that controls those core transcription factors, it’s right at the heart of the regulatory process of pluripotency,” said Blencowe.    At the same time, the mechanism represses the genes required for differentiation – the process whereby by a stem cell loses “stemness” and becomes a specific cell type that makes up an organ or performs a function.


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