Journal
CELL STEM CELL
Volume 13, Issue 3, Pages 314-327Publisher
CELL PRESS
DOI: 10.1016/j.stem.2013.06.018
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Funding
- EMBO Postdoctoral Fellowship
- National Institutes of Health NIAMS [R01AR31737]
- New York State Department of Health [NYSTEM/C026427]
- NIH/NIMH [R21MH099452]
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In adult skin, self-renewing, undifferentiated hair follicle stem cells (HF-SCs) reside within a specialized niche, where they spend prolonged times as a single layer of polarized, quiescent epithelial cells. When sufficient activating signals accumulate, HF-SCs become mobilized to fuel tissue regeneration and hair growth. Here, we show that architectural organization of the HF-SC niche by transcription factor LHX2 plays a critical role in HF-SC behavior. Using genome-wide chromatin and transcriptional profiling of HF-SCs in vivo, we show that LHX2 directly transactivates genes that orchestrate cytoskeletal dynamics and adhesion. Conditional ablation of LHX2 results in gross cellular disorganization and HF-SC polarization within the niche. LHX2 loss leads to a failure to maintain HF-SC quiescence and hair anchoring, as well as progressive transformation of the niche into a sebaceous gland. These findings suggest that niche organization underlies the requirement for LHX2 in hair follicle structure and function.
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