@article{493b2e16350b46728cc51cf3827440bd,
title = "NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices",
abstract = "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.",
author = "Adam, {Rene C.} and Hanseul Yang and Yejing Ge and Infarinato, {Nicole R.} and Shiri Gur-Cohen and Yuxuan Miao and Ping Wang and Yilin Zhao and Lu, {Catherine P.} and Kim, {Jeong E.} and Ko, {Joo Y.} and Paik, {Seung S.} and Gronostajski, {Richard M.} and Jaehwan Kim and Krueger, {James G.} and Deyou Zheng and Elaine Fuchs",
note = "Funding Information: We thank E. Wong, M. Nikolova, J. Racelis and P. Nasseir for technical assistance, and L. Polak, J. Levorse and L. Hidalgo for assistance with mouse handling and experiments. We thank The Rockefeller University FACS facility for cell sorting, the Rockefeller Genomics Resource Center and Weill Cornell Genomics Resource Center for high-throughput sequencing, and the Comparative Bioscience Center (AAALAC accredited) for the care of mice in accordance with National Institutes of Health guidelines. E.F. is an investigator of the Howard Hughes Medical Institute. R.C.A. was the recipient of an Anderson Cancer Center Graduate Fellowship. H.Y. was the recipient of a Kwanjeong Educational Foundation Graduate Fellowship. Y.G. was a postdoctoral fellow of the American Federation of Aging Research. N.R.I. is the recipient of a National Institutes of Health Predoctoral National Research Service Award F31 Fellowship from NIAMS. This work was supported by grants from the National Institutes of Health to E.F. (R01-AR31737). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = jun,
day = "1",
doi = "10.1038/s41556-020-0513-0",
language = "English (US)",
volume = "22",
pages = "640--650",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "6",
}