Findlay lab discovers “molecular switch” that controls stem cell differentiation

Published on 3 July 2017

Research by Rosalia Fernandez-Alonso, a post-doctoral investigator in Dr. Greg Findlay’s lab in the MRC-PPU, has been published in and featured on the cover of the July edition of the journal EMBO Reports.

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The paper identifies a new type of molecular switch involving BET bromodomain proteins, which enables embryonic stem (ES) cells to differentiate into mesendoderm, an important precursor cell that gives rise to tissues and organs such as pancreas, liver, heart and blood. Rosalia found that members of the BET protein family drive distinct patterns of signalling and gene expression, such that interchange between BET proteins in ES cells coordinates the process of mesendoderm formation.

“A key challenge in the field is understanding the molecular events that drive ES cells to exit the stem cell state and initiate the process of forming functional tissues”, said Greg Findlay, the senior author on this publication. “Rosalia’s findings shed significant new light on this important question, and could have implications for how we go about developing tissue replacement therapies in the lab. For example, the research shows how BET proteins control regeneration of liver and pancreas, which will potentially allow us to manipulate this key regenerative pathway using chemicals”.

Although the Findlay lab spearheaded the project, several groups in the School of Life Sciences collaborated on this paper, including those of Alessio Ciulli (BCDD), Angus Lamond (GRE) and Gopal Sapkota (MRC-PPU), as well as the Human Pluripotent Stem Cell facility. The work in the Findlay lab was supported by an MRC New Investigator Research Grant  and Tenovus Scotland research grant.

You can read a copy of the paper here: Fernandez‐Alonso et al (2017) Brd4‐Brd2 isoform switching coordinates pluripotent exit and Smad2‐dependent lineage specification

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