ArticleProceedings of the National Academy of Sciences of the United States of America2016
FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 165 citations in OpenAlex.
- New insights into diagnostic values and mechanisms of ferroptosis associated with immune infiltration in diabetic kidney disease.Experimental and therapeutic medicine · 2026Article
- Article
- FOXC1 Controls Smooth Muscle Cell Differentiation and Plasticity in Vascular Disease.JACC. Basic to translational science · 2026Article
- Roles of Msx2 in exogen control: modulating the stem cell niche during the transition from hair shedding to regeneration.Journal of advanced research · 2026Article
- An updated guide to hair follicle stem cell markers and changes in their expression with aging.JID innovations : skin science from molecules to population health · 2026Review
- Scar Inhibition in Wound Healing: Mechanisms, Design, and Recent Advances.Exploration (Beijing, China) · 2026Review
- Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity.Cell · 2026Article
- H2AK119ub dynamics control hair follicle stem cell quiescence.Nature communications · 2025Article
- Lifting regenerative barriers promotes epithelial cell fate plasticity supporting lineage conversion.Nature communications · 2025Article
- Epigenomic regulation of stemness contributes to the low immunogenicity of the most mutated human cancer.Cell reports · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Di-Genic Inheritance in Genodermatoses: Insights from Two Consanguineous Cases in a Reference Lebanese Center within the Middle East and North Africa (MENA) Region.Dermatology practical & conceptual · 2025Article
- Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration.Cell · 2024Article
- N6-methyladenosine (m6A)-circHECA from secondary hair follicle of cashmere goats: identification, regulatory network and expression regulated potentially by methylation of its host gene promoter.Animal bioscience · 2024Article
- Article
- Pleiotropy in FOXC1-attributable phenotypes involves altered ciliation and cilia-dependent signaling.Scientific reports · 2024Article
- Ontogeny of Skin Stem Cells and Molecular Underpinnings.Current issues in molecular biology · 2024Review
- Reprofiling synthetic glucocorticoid-induced leucine zipper fusion peptide as a novel and effective hair growth promoter.Archives of dermatological research · 2024Article
- Review
- Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices.Science (New York, N.Y.) · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.