OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF in mouse ESCs

Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E. Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel-Gutfreund, Mehdi Khaled, Jacob H. Hanna, Carmit Levy

Research output: Contribution to journalArticlepeer-review

Abstract

Ectopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has not been systemically examined. Here we discover that amongst different developmental stages, mouse embryonic stem cells (mESCs) are resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. By generating a transgenic system we exhibit that in mESCs, the pluripotency master regulator Oct4, counteracts pro-differentiation induced by Mitf by physical interference with MITF transcriptional activity. We further demonstrate that mESCs must be released from Oct4-maintained pluripotency prior to ectopically induced differentiation. Moreover, Oct4 induction in various differentiated cells represses their lineage identity in vivo. Alongside, chromatin architecture combined with ChIP-seq analysis suggest 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.

Original languageEnglish
Article number1022
Number of pages12
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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