RT Journal Article
SR Electronic
T1 OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 142943
DO 10.1101/142943
A1 Danna Sheinboim
A1 Itay Maza
A1 Iris Dror
A1 Shivang Parikh
A1 Vladislav Krupalnik
A1 Rachel E Bell
A1 Asaf Zviran
A1 Yusuke Suita
A1 Ofir Hakim
A1 Yael Mandel Gutfreund
A1 Mehdi Khaled
A1 Jacob H Hanna
A1 Carmit Levy
YR 2017
UL http://biorxiv.org/content/early/2017/05/27/142943.abstract
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.