A genome-wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key mediator of differentiation
Bart A Westerman, A Koen Braat, Nicole Taub, Marko Potman, Joseph HA Vissers, Marleen Blom, Els Verhoeven, Hans Stoop, Ad Gillis, Arno Velds, Wouter Nijkamp, Roderick Beijersbergen, Lukas A Huber, Leendert HJ Looijenga, Maarten van Lohuizen
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2011
Despite intense investigation of intrinsic and extrinsic factors that regulate pluripotency, the process of initial fate commitment of embryonic stem (ES) cells is still poorly understood. We used a genome-wide short hairpin RNA screen in mouse ES cells to identify genes that are essential for initiation of differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1, also known as Lamtor3 or Map2k1ip1) stimulated self-renewal of ES cells, blocked differentiation, and promoted proliferation. Fibroblast growth factor 4 (FGF4) signaling is required for initial fate commitment of ES cells. Knockdown of Mp1 inhibited FGF4-induced differentiation but did not alter FGF4-driven ..View full abstract
Awarded by FWF Science Fund, Austria
The Dutch Cancer Society supported this work. Work in the Huber laboratory was supported by the SFB021 Cell Proliferation and Cell Death in Tumors of the FWF Science Fund, Austria.