TY - JOUR
T1 - Architectural niche organization by LHX2 is linked to hair follicle stem cell function
AU - Folgueras, Alicia R.
AU - Guo, Xingyi
AU - Pasolli, H. Amalia
AU - Stokes, Nicole
AU - Polak, Lisa
AU - Zheng, Deyou
AU - Fuchs, Elaine
N1 - Funding Information:
We thank S. Dewell for assistance in high-throughput sequencing and analysis (RU Genomics Resource Center); S. Mazel, L. Li, S. Semova, and S. Tadesse for FACS sorting (RU FACS facility); the RU Bioimaging Center for advice on image acquisition; and the MSKCC Genomics Core Facility for RNA and microarray processing. We thank E.F.’ laboratory members D. Oristian and A. Aldeguer for assistance in mouse research; E. Heller for advice on image analyses and quantifications; M. Nikolova, J. Racelis, S. Chai, E. Wong, and P. Janki for technical assistance; and W.-H. Lien, C. Luxenburg, M. Kadaja, B. Keyes, and C.P. Lu for valuable discussions. A.R.F. was supported by an EMBO Postdoctoral Fellowship. E.F. is an HHMI Investigator. This work was supported by grants to E.F. (National Institutes of Health NIAMS R01AR31737 and New York State Department of Health NYSTEM/C026427) and to D.Z. (NIH/NIMH R21MH099452).
PY - 2013/9/5
Y1 - 2013/9/5
N2 - 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.
AB - 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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U2 - 10.1016/j.stem.2013.06.018
DO - 10.1016/j.stem.2013.06.018
M3 - Article
C2 - 24012369
AN - SCOPUS:84884143214
VL - 13
SP - 314
EP - 327
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 3
ER -