AI Article Synopsis
- The study investigates how specific lineage master regulators can influence cell fate transitions during development, particularly focusing on mouse embryonic stem cells (mESCs).
- It finds that the pluripotency master regulator Oct4 inhibits differentiation induced by MITF, a melanocyte regulator, by interfering with MITF’s ability to activate genes necessary for that differentiation.
- The research highlights the importance of releasing mESCs from Oct4's control before differentiation can occur, suggesting new insights for regenerative medicine by revealing the competitive interactions between Oct4 and lineage master regulators.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647326 | PMC |
| http://dx.doi.org/10.1038/s41467-017-01122-1 | DOI Listing |
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