NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
- Title
- NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices
- Author
- 김정은
- Keywords
- HAIR FOLLICLE; NICHE; QUIESCENCE; GENERATION; MATURATION; PROTEINS; PATHWAYS; DYNAMICS; SKIN; SEQ
- Issue Date
- 2020-05
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE CELL BIOLOGY, v. 22, no. 6, page. 640-650
- Abstract
- Adam, Yang et al. show that the transcription factors NFIB and NFIX promote stemness by establishing chromatin accessibility and regulating the super-enhancers that govern bulge stem cell identity. 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.
- URI
- https://www.nature.com/articles/s41556-020-0513-0https://repository.hanyang.ac.kr/handle/20.500.11754/166421
- ISSN
- 1476-4679; 1465-7392
- DOI
- 10.1038/s41556-020-0513-0
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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