title: Architectural niche organization by LHX2 is linked to hair follicle stem cell function.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Folgueras
authors.forename: Xingyi
authors.initials: X
authors.lastname: Guo
authors.forename: H Amalia
authors.initials: HA
authors.lastname: Pasolli
authors.forename: Nicole
authors.initials: N
authors.lastname: Stokes
authors.forename: Lisa
authors.initials: L
authors.lastname: Polak
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D003599:Cytoskeleton / Q000378:metabolism; D020869:Gene Expression Profiling; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D012038:Regeneration; D012627:Sebaceous Glands / Q000502:physiology*; D055153:Stem Cell Niche / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors