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bioRxiv · 10.1101/013961

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

Asaf Zviran·Yoach Rais·Nofar Mor·Noa Novershtern·Jacob H Hanna
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Abstract

Our group has published a study on induced pluripotent stem cell (iPSC) reprogramming (Rais et al. Nature 20131) that reached the following conclusions: a) Mbd3/NuRD is a repressor of inducing naive 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 naive pluripotency conditions (2i supplement applied only after 48 hours, human LIF, hypoxia and Vitamin C containing Knockout serum replacement)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 reprogramming2,3. 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 colleagues2,3, and reconfirms that Mbd3/NuRD is a major pathway that inhibits the maintenance and induction of pluripotency1. Further, we foresee that its controlled manipulation is likely to become an integral pathway for inducing and maintaining naive pluripotency in a variety of species.

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Asaf Zviran, Yoach Rais, Nofar Mor, Noa Novershtern, Jacob H Hanna. 2015-03-06. Mbd3/NuRD is a Key Inhibitory Module During the Induction and Maintenance of Naïve Pluripotency. https://doi.org/10.1101/013961

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