Mar 6, 2015

Mbd3/NuRD is a Key Inhibitory Module During the Induction and Maintenance of Naïve Pluripotency

BioRxiv : the Preprint Server for Biology
Asaf ZviranJacob H Hanna

Abstract

Our group has published a study on induced pluripotent stem cell (iPSC) reprogramming (Rais et al. Nature 2013[1][1]) that reached the following conclusions: a) Mbd3/NuRD is a repressor of inducing naïve pluripotency from mouse Epiblast stem cells (EpiSCs), primordial germ cells (PGCs), murine somatic cells and human secondary fibroblasts; b) Up to 100% iPSC formation efficiency can be achieved via optimized Mbd3/NuRD depletion, in concert with optimized OKSM delivery and naïve pluripotency conditions (2i supplement applied only after 48 hours, human LIF, hypoxia and Vitamin C containing Knockout serum replacement)[1][1]. This represented the first proof for deterministic/near-deterministic iPSC reprogramming, and highlighted a previously unappreciated role for Mbd3/NuRD in hampering the re-establishment of pluripotency. Recent reports have seemingly provided contradictory results and attempted to dispute our iPSC efficiency quantifications and/or the role of Mbd3/NuRD in blocking reprogramming[2][2],[3][3]. Here we provide a detailed response to these reports based on extended discussions and providing new data. The synthesis presented herein disagrees with claims made by Silva, Hendrich, Bertone and colleagues[2][2],[3][3], a...Continue Reading

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Mentioned in this Paper

Study
Mapk Cascade Involved in Cell Wall Biogenesis
Biochemical Pathway
Transcription Repressor/Corepressor
Specimen Type - Fibroblasts
Pluripotent Stem Cells
LIF
Murine
Phage Display Peptide Library
Knock-out

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