NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
10
09
2019
accepted:
30
03
2020
pubmed:
13
5
2020
medline:
17
9
2020
entrez:
13
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32393888
doi: 10.1038/s41556-020-0513-0
pii: 10.1038/s41556-020-0513-0
pmc: PMC7367149
mid: NIHMS1580746
doi:
Substances chimiques
Chromatin
0
NFI Transcription Factors
0
Nfib protein, mouse
0
Nfix protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
640-650Subventions
Organisme : NCI NIH HHS
ID : R00 CA237859
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA237859
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR031737
Pays : United States
Organisme : NIAMS NIH HHS
ID : F31 AR073110
Pays : United States
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