NFATc1 Balances Quiescence and Proliferation of Skin Stem Cells
Open accessAbstract
Quiescent adult stem cells reside in specialized niches where they become activated to proliferate and differentiate during tissue homeostasis and injury. How stem cell quiescence is governed is poorly understood. We report here that NFATc1 is preferentially expressed by hair follicle stem cells in their niche, where its expression is activated by BMP signaling upstream and it acts downstream to transcriptionally repress CDK4 and maintain stem cell quiescence. As stem cells become activated during hair growth, NFATc1 is downregulated, relieving CDK4 repression and activating proliferation. When calcineurin/NFATc1 signaling is suppressed, pharmacologically or via complete or conditional NFATc1 gene ablation, stem cells are activated prematurely, resulting in precocious follicular growth. Our findings may explain why patients receiving cyclosporine A for immunosuppressive therapy display excessive hair growth, and unveil a functional role for calcium-NFATc1-CDK4 circuitry in governing stem cell quiescence.
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NFATC1 expression was predominantly cytoplasmic, consistent with follicular bulges in foetal skin; adult bulge cells displayed nuclear NFATC1 expression, a sign of maturity.
“The expression pattern of NFATC1 was predominantly cytoplasmic, which was consistent with follicular bulges in foetal skin; by contrast, adult bulge cells displayed nuclear NFATC1 expression, a sign of maturity (Extended Data Fig. 10)2,36.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [36]
Skin organoid HFs are capable of producing nascent HFSCs, reminiscent of HFSCs at a late embryonic (~E17.5) stage of development.
“Based on previous studies, these data suggest that skin organoid HFs are capable of producing nascent HFSCs, reminiscent of HFSCs at a late embryonic (~E17.5) stage of development (Horsley et al., 2008).”
From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Horsley et al., 2008
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References 62 · Cited by 424
- Authors
- Horsley, V., Aliprantis, A. O., Polak, L., Glimcher, L. H., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 132
- Issue
- 2
- Pages
- 299-310
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2546702
- OpenAlex
- W2139867317
- Cited by
- 424
- References
- 62
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 24 · 2021: 29 · 2020: 23 · 2019: 17 · 2018: 27 · 2017: 19 · 2016: 19 · 2015: 30 · 2014: 24 · 2013: 30 · 2012: 27
- FWCI
- 42.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2060 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2r01ar050452-21)
- National Institute of Allergy and Infectious Diseases (AI-31541, U19AI031541, P01AI031541)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR31737, K99AR054775, R01AR031737, R01-AR050452)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- NFATc1, hair follicle stem cells, stem cell quiescence, stem cell proliferation, BMP signaling, calcineurin, skin stem cells, hair growth, cyclosporine, transcriptional repression
- MeSH terms
- Animals, Cell Nucleus, Cells, Cultured, Embryo, Mammalian, Immunohistochemistry, Immunosuppressive Agents, Mice, Nude, Morphogenesis, Retroviridae, RNA, Messenger, Skin, Stem Cells, Transcription Factors, Transplantation, Homologous, Biomarkers, Down-Regulation, Gene Expression, Skin Transplantation, Cyclosporine, Gene Deletion, Genes, Reporter, Mice, Knockout, Gene Expression Regulation, Developmental, Hair Follicle, Antigens, CD34, Transgenes, Cell Proliferation, NFATC Transcription Factors, Cyclin-Dependent Kinase 4, Mice
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