Other
17 Authors
- Krueger JG,
- Zhao Y,
- Zheng D,
- Adam RC,
- Paik SS,
- Kim JE,
- Gur-Cohen S,
- Wang P,
- Lu CP,
- Ge Y,
- Fuchs E,
- Infarinato NR,
- Kim J,
- Gronostajski RM,
- Miao Y,
- Ko JY,
- Yang H
| First Author | Adam RC | Year | 2020 |
| Journal | Nat Cell Biol | Volume | 22 |
| Issue | 6 | Pages | 640-650 |
| PubMed ID | 32393888 | Mgi Jnum | J:291088 |
| Mgi Id | MGI:6442635 | Doi | 10.1038/s41556-020-0513-0 |
| Citation | Adam RC, et al. (2020) NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices. Nat Cell Biol 22(6):640-650 |
| abstractText | 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. |
