Capturing and profiling adult hair follicle stem cells
Abstract
The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells. We show that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling. After isolation, adult Krt1-15-EGFP-positive cells reconstituted all components of the cutaneous epithelium and had a higher proliferative potential than Krt1-15-EGFP-negative cells. Genetic profiling of hair follicle stem cells revealed several known and unknown receptors and signaling pathways important for maintaining the stem cell phenotype. Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair.
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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 Morris et al., 2004
Quiescent stem cells that regenerate hair follicles reside in the bulge.
“Quiescent stem cells that are responsible for regenerating the hair follicles lie within the bulge of the hair follicles21,31,32”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [31]
Initiation of a new anagen cycle depends upon activation of a small number of quiescent stem cells that reside in the bulge.
“Initiation of a new anagen cycle depends upon activation of a small number of quiescent stem cells that reside in the bulge, a niche at the follicle base15–19.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [19]
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Aoki, H., Hara, A., Motohashi, T., & Kunisada, T. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.155 · Cited by 40 · see citing works
State-dependent signaling by Ca<sub>v</sub>1.2 regulates hair follicle stem cell function
Yucel, G., Altindag, B., Gomez-Ospina, N., Rana, A., Panagiotakos, G., Lara, M. F., Dolmetsch, R., & Oro, A. E. (2013) · Genes & Development · doi:10.1101/gad.216556.113 · Cited by 31 · see citing works
Advancing insights into stem cell niche complexities with next-generation technologies
Heitman, N., Saxena, N., & Rendl, M. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2018.06.012 · Cited by 31 · see citing works
- Authors
- Morris, R. J., Liu, Y., Marles, L., Yang, Z., Trempus, C., Li, S., Lin, J. S., Sawicki, J. A., & Cotsarelis, G.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Columbia University (US)
- Main Line Health (US)
- Corresponding author
- Cotsarelis, George
- Venue
- Nature Biotechnology
- Published
- 2004-03-14
- Volume
- 22
- Issue
- 4
- Pages
- 411-417
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2020969391
- Cited by
- 1,283
- References
- 45
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 33 · 2023: 24 · 2022: 41 · 2021: 47 · 2020: 59 · 2019: 46 · 2018: 46 · 2017: 54 · 2016: 60 · 2015: 39 · 2014: 63 · 2013: 83 · 2012: 87
- FWCI
- 84.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA97957, R01CA097957)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR46837, R01AR046837)
- 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, Cre recombinase, lineage tracing, cell isolation, hair cycle, stem cell proliferation, stem cell signaling pathways, hair loss treatment
- MeSH terms
- Animals, Cell Division, Cell Line, Cell Separation, Epithelial Cells, Fibroblasts, Flow Cytometry, Genetic Techniques, Luminescent Proteins, Mice, Transgenic, Promoter Regions, Genetic, RNA, RNA, Messenger, Stem Cells, Transcription, Genetic, Keratinocytes, Up-Regulation, 3T3 Cells, DNA, Complementary, Hair Follicle, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Recombinases, Green Fluorescent Proteins, Mice
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