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Confirmatory Results

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
doi: https://doi.org/10.1101/013961
Asaf Zviran
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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Yoach Rais
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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Nofar Mor
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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Noa Novershtern
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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  • For correspondence: Jacob.hanna@weizmann.ac.il noa.novershtern@weizmann.ac.il
Jacob H. Hanna
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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  • For correspondence: Jacob.hanna@weizmann.ac.il noa.novershtern@weizmann.ac.il
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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 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. 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 naïve pluripotency in a variety of species.

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Posted March 06, 2015.
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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
bioRxiv 013961; doi: https://doi.org/10.1101/013961
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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
bioRxiv 013961; doi: https://doi.org/10.1101/013961

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