期刊
CELL STEM CELL
卷 24, 期 2, 页码 271-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.12.012
关键词
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资金
- NIH [P50-HG007735, R01GM109836, F32AR070565]
- California Institute for Regenerative Medicine tools [RT3-07796]
- National Natural Science Foundation of China [61671444, 61621003, 91730301]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB13000000]
- EB Research Partnership
Tissue development results from lineage-specific transcription factors (TFs) programming a dynamic chromatin landscape through progressive cell fate transitions. Here, we define epigenomic landscape during epidermal differentiation of human pluripotent stem cells (PSCs) and create inference networks that integrate gene expression, chromatin accessibility, and TF binding to define regulatory mechanisms during keratinocyte specification. We found two critical chromatin networks during surface ectoderm initiation and keratinocyte maturation, which are driven by TFAP2C and p63, respectively. Consistently, TFAP2C, but not p63, is sufficient to initiate surface ectoderm differentiation, and TFAP2C-initiated progenitor cells are capable of maturing into functional keratinocytes. Mechanistically, TFAP2C primes the surface ectoderm chromatin landscape and induces p63 expression and binding sites, thus allowing maturation factor p63 to positively autoregulate its own expression and close a subset of the TFAP2-Cinitiated surface ectoderm program. Our work provides a general framework to infer TF networks controlling chromatin transitions that will facilitate future regenerative medicine advances.
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