Open AccessNFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
Author(s) -
René Adam,
Hanseul Yang,
Yejing Ge,
Nicole R. Infarinato,
Shiri Gur-Cohen,
Yanying Miao,
Ping Wang,
Yilin Zhao,
Catherine P. Lu,
Jeong Eun Kim,
Joo Yeon Ko,
Seung Sam Paik,
Richard M. Gronostajski,
Jaehwan Kim,
James G. Krueger,
Deyou Zheng,
Elaine Fuchs
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-0513-0
Subject(s) - biology , transcription factor , chromatin , microbiology and biotechnology , crosstalk , epigenome , enhancer , epigenetics , cell fate determination , stem cell , polycomb group proteins , genetics , gene , dna methylation , gene expression , physics , repressor , optics
Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.