PT  - JOURNAL ARTICLE
AU  - Danna Sheinboim
AU  - Itay Maza
AU  - Iris Dror
AU  - Shivang Parikh
AU  - Vladislav Krupalnik
AU  - Rachel E Bell
AU  - Asaf Zviran
AU  - Yusuke Suita
AU  - Ofir Hakim
AU  - Yael Mandel Gutfreund
AU  - Mehdi Khaled
AU  - Jacob H Hanna
AU  - Carmit Levy
TI  - OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF
AID  - 10.1101/142943
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 142943
4099  - http://biorxiv.org/content/early/2017/05/27/142943.short
4100  - http://biorxiv.org/content/early/2017/05/27/142943.full
AB  - Ectopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has never been systemically examined. Here we discovered that amongst different developmental stages, embryonic stem cells (ESCs) were resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. We generated a transgenic system and found that in ESCs, the pluripotency master regulator, OCT4, counteracts pro-differentiation induced by MITF by physical interference with MITF transcriptional activity. We further found that ESCs must be released from OCT4-maintained pluripotency prior to ectopically induced differentiation. Moreover, OCT4 induction in various differentiated cells repressed their lineage identity in vivo. Alongside, chromatin architecture combined with ChIP-seq analysis suggested that OCT4 competes with various lineage master regulators for binding promoters and enhancers. Our analysis reveals pluripotency and transdifferentiation regulatory principles and could open new opportunities in the field of regenerative medicine.