JARID2-associated protein network drives rapid and efficient reprogramming to pluripotency.

Somatic cell reprogramming can be achieved by cell fusion with embryonic stem cells (ESCs), nuclear transfer into oocytes, or forced expression of transcription factors essential for ESC identity. Reprogramming by transcription factors is a less efficient and slower process than that by other methods. Identification of a gene set capable of driving rapid and proper reprogramming to induced pluripotent stem cells (iPSCs) is an important issue. Here, we show that the efficiency and kinetics of iPSC reprogramming are dramatically improved by combined transduction of Jarid2, a gene highly expressed in both ESCs and oocytes and genes encoding its associated proteins. We demonstrate that forced expression of Jarid2 promotes iPSC reprogramming by suppressing the expression of Arf, a known reprogramming barrier, and that the N-terminal half of JARID2 is sufficient for such promotion. Moreover, Jarid2 accelerated retroviral transgene silencing and Nanog promoter demethylation, confirming its promoting activity. We further reveal that JARID2 physically interacts with ESRRB, SALL4A and PRDM14, and show that these JARID2-associated proteins synergistically and robustly facilitate iPSC reprogramming in a Jarid2-dependent manner. Our findings provide an insight into the important roles of Jarid2 during reprogramming, and suggest that the JARID2-associated protein network contributes to overcoming reprogramming barriers.

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