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
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.
UR - http://www.scopus.com/inward/record.url?scp=84884143214&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884143214&partnerID=8YFLogxK
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 -