Esrrb Is a Pivotal Target of the Gsk3/Tcf3 Axis Regulating Embryonic Stem Cell Self-Renewal

Embryonic stem cells (ESCs) can give rise to every cell type of the body, an ability called pluripotency. For this reason they hold great promise for drug development and regenerative medicine. Crucially, ESCs are able to self-renew (the technical term for stem cells dividing to generate more stem cells), which allows researchers to multiply them in unlimited quantities. How self-renewal is controlled has been something of a mystery. This study identifies a previously unrecognised regulatory pathway at the heart of ESC self-renewal.  Specifically, the researchers found that a transcription factor called Esrrb controls gene expression in ESCs and is directly connected to a cellular signaling pathway. This discovery was greatly facilitated by development of new data-mining infrastructure within the Wellcome Trust – MRC Cambridge Stem Cell Institute, which will now be available as a public resource.  Dr Graziano Martello, first author of the paper, commented: “These findings expand our understanding of how the behavior of ESCs is controlled bythe environment, bringing us close to harnessing their potential for medical advances.”

The research project has been an international collaborative effort, involving the teams of Prof. Austin Smith and Dr Bertie Gottgens at the Wellcome Trust – MRC Cambridge Stem Cell Institute, and Hitoshi Niwa from the RIKEN Center for Developmental Biology in Kobe in Japan. The important link with Dr Niwa was supported through a BBSRC Japan/UK Partnering Award.

Publication details:

Esrrb Is a Pivotal Target of the Gsk3/Tcf3 Axis Regulating Embryonic Stem Cell Self-Renewal.

Cell Stem Cell, Volume 11, Issue 4, 491-504, 5 October 2012

Mouse Embryonic Stem cells (green) re-enter development after being introduced in an early embryo

Mouse Embryonic Stem cells (green) re-enter development after being introduced in an early embryo (Credit: Graziano Martello)

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