Cited by 554Hair Growth and DisordersSkin and Cellular Biology Researchdental development and anomalies

Hair follicle stem cells are specified and function in early skin morphogenesis

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Nowak, Jonathan A., Polak, Lisa, Pasolli, H. Amalia, Fuchs, Elaine·2008·Cell Stem Cell

Abstract

In adult skin, epithelial hair follicle stem cells (SCs) reside in a quiescent niche and are essential for cyclic bouts of hair growth. Niche architecture becomes pronounced postnatally at the start of the first hair cycle. Whether SCs exist or function earlier is unknown. Here we show that slow-cycling cells appear early in skin development, express SC markers, and later give rise to the adult SC population. To test whether these early slow-cycling cells function as SCs, we use Sox9-Cre for genetic marking and K14-Cre to embryonically ablate Sox9, an essential adult SC gene. We find that the progeny of Sox9-expressing cells contribute to all skin epithelial lineages and Sox9 is required for SC specification. In the absence of early SCs, hair follicle and sebaceous gland morphogenesis is blocked, and epidermal wound repair is compromised. These findings establish the existence of early hair follicle SCs and reveal their physiological importance in tissue morphogenesis.

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Crossref · 10.1016/j.stem.2008.05.009

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  • KRT15 and SOX9 were expressed broadly in the organoid HF outer root sheath as well as the bulge-like region.

    “We found that the HF bulge and epithelial stem cells markers, KRT15 and SOX9, were expressed broadly in the organoid HF outer root sheath as well as the bulge-like region (Morris et al., 2004; Nowak et al., 2008; Figure 6B–B″″).”

    From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Nowak et al., 2008

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  1. Akiyama H Kim JE Nakashima K Balmes G Iwai N Deng JM Zhang Z Martin JF Behringer RR Nakamura T Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc Natl Acad Sci U S A 2005 102 14665 14670 16203988 PMC1239942
  2. Akiyama H Lyons JP Mori-Akiyama Y Yang X Zhang R Zhang Z Deng JM Taketo MM Nakamura T Behringer RR Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 2004 18 1072 1087 15132997 PMC406296
  3. Blanpain C Fuchs E Epidermal stem cells of the skin. Annual review of cell and developmental biology 2006 22 339 373 PMC2405915 16824012
  4. Blanpain C Lowry WE Geoghegan A Polak L Fuchs E Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 2004 118 635 648 15339667
  5. Braun KM Niemann C Jensen UB Sundberg JP Silva-Vargas V Watt FM Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis. Development 2003 130 5241 5255 12954714
  6. Cotsarelis G Epithelial stem cells: a folliculocentric view. J Invest Dermatol 2006 126 1459 1468 16778814
  7. Horsley V Aliprantis AO Polak L Glimcher LH Fuchs E NFATc1 balances quiescence and proliferation of skin stem cells. Cell 2008 132 299 310 18243104 PMC2546702
  8. Horsley V O'Carroll D Tooze R Ohinata Y Saitou M Obukhanych T Nussenzweig M Tarakhovsky A Fuchs E Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell 2006 126 597 609 16901790 PMC2424190
  9. Ito M Kizawa K Hamada K Cotsarelis G Hair follicle stem cells in the lower bulge form the secondary germ, a biochemically distinct but functionally equivalent progenitor cell population, at the termination of catagen. Differentiation; research in biological diversity 2004 72 548 557 15617565
  10. Ito M Liu Y Yang Z Nguyen J Liang F Morris RJ Cotsarelis G Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nature medicine 2005 11 1351 1354 16288281
  11. Kaufman CK Zhou P Pasolli HA Rendl M Bolotin D Lim KC Dai X Alegre ML Fuchs E GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev 2003 17 2108 2122 12923059 PMC196453
  12. Levy V Lindon C Harfe BD Morgan BA Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev Cell 2005 9 855 861 16326396
  13. Levy V Lindon C Zheng Y Harfe BD Morgan BA Epidermal stem cells arise from the hair follicle after wounding. Faseb J 2007 21 1358 1366 17255473
  14. Liu Y Lyle S Yang Z Cotsarelis G Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 2003 121 963 968 14708593
  15. Mao X Fujiwara Y Orkin SH Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice. Proc Natl Acad Sci U S A 1999 96 5037 5042 10220414 PMC21812
  16. Maretto S Cordenonsi M Dupont S Braghetta P Broccoli V Hassan AB Volpin D Bressan GM Piccolo S Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci U S A 2003 100 3299 3304 12626757 PMC152286
  17. Moore KA Lemischka IR Stem cells and their niches. Science 2006 311 1880 1885 16574858
  18. Morris RJ Liu Y Marles L Yang Z Trempus C Li S Lin JS Sawicki JA Cotsarelis G Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 2004 22 411 417 15024388
  19. Morris RJ Potten CS Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. J Invest Dermatol 1999 112 470 475 10201531
  20. Nguyen H Rendl M Fuchs E Tcf3 governs stem cell features and represses cell fate determination in skin. Cell 2006 127 171 183 17018284
  21. Oshima H Rochat A Kedzia C Kobayashi K Barrandon Y Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 2001 104 233 245 11207364
  22. Rendl M Lewis L Fuchs E Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLoS Biol 2005 3 e331 16162033 PMC1216328
  23. Rhee H Polak L Fuchs E Lhx2 maintains stem cell character in hair follicles. Science 2006 312 1946 1949 16809539 PMC2405918
  24. Schmidt-Ullrich R Paus R Molecular principles of hair follicle induction and morphogenesis. Bioessays 2005 27 247 261 15714560
  25. Stenn KS Paus R Controls of hair follicle cycling. Physiol Rev 2001 81 449 494 11152763
  26. Taylor G Lehrer MS Jensen PJ Sun TT Lavker RM Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 2000 102 451 461 10966107
  27. Trempus CS Morris RJ Bortner CD Cotsarelis G Faircloth RS Reece JM Tennant RW Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. J Invest Dermatol 2003 120 501 511 12648211
  28. Tumbar T Guasch G Greco V Blanpain C Lowry WE Rendl M Fuchs E Defining the epithelial stem cell niche in skin. Science 2004 303 359 363 14671312 PMC2405920
  29. Vasioukhin V Degenstein L Wise B Fuchs E The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc Natl Acad Sci U S A 1999 96 8551 8556 10411913 PMC17554
  30. Vidal VP Chaboissier MC Lutzkendorf S Cotsarelis G Mill P Hui CC Ortonne N Ortonne JP Schedl A Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment. Curr Biol 2005 15 1340 1351 16085486

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Authors
Nowak, J. A., Polak, L., Pasolli, H. A., & Fuchs, E.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Fuchs, Elaine
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2008-07
Volume
3
Issue
1
Pages
33-43
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W1998479150
Cited by
554
References
3
Citations by year
2026: 18 · 2025: 17 · 2024: 18 · 2023: 25 · 2022: 27 · 2021: 29 · 2020: 30 · 2019: 35 · 2018: 31 · 2017: 25 · 2016: 25 · 2015: 38 · 2014: 45 · 2013: 41 · 2012: 52
FWCI
39.40
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (2r01ar050452-21)
  • Langley Research Center
  • National Cancer Institute (T32CA009673)
  • National Institute of General Medical Sciences (T32GM007739)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR031737, R01-AR050452)
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
Keywords
hair follicle stem cells, skin morphogenesis, SOX9, slow-cycling cells, stem cell specification, hair follicle morphogenesis, stem cell niche
MeSH terms
Adult, Animals, Cell Cycle, Epithelial Cells, High Mobility Group Proteins, Humans, Morphogenesis, Skin, Skin Physiological Phenomena, Stem Cells, Transcription Factors, Wound Healing, Biomarkers, Hair Follicle, Integrases, Stem Cell Transplantation, Mice, SOX9 Transcription Factor

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