Manipulation of stem cell proliferation and lineage commitment:visualisation of label-retaining cells in wholemounts of mouse epidermis
Abstract
Mammalian epidermis is maintained by stem cells that have the ability to self-renew and generate daughter cells that differentiate along the lineages of the hair follicles, interfollicular epidermis and sebaceous gland. As stem cells divide infrequently in adult mouse epidermis, they can be visualised as DNA label-retaining cells (LRC). With whole-mount labelling, we can examine large areas of interfollicular epidermis and many hair follicles simultaneously, enabling us to evaluate stem cell markers and examine the effects of different stimuli on the LRC population. LRC are not confined to the hair follicle, but also lie in sebaceous glands and interfollicular epidermis. LRC reside throughout the permanent region of the hair follicle,where they express keratin 15 and lie in a region of high α6β4 integrin expression. LRC are not significantly depleted by successive hair growth cycles. They can, nevertheless, be stimulated to divide by treatment with phorbol ester, resulting in near complete loss of LRC within 12 days. Activation of Myc stimulates epidermal proliferation without depleting LRC and induces differentiation of sebocytes within the interfollicular epidermis. Expression of N-terminally truncated Lef1 to block β-catenin signalling induces transdifferentiation of hair follicles into interfollicular epidermis and sebocytes and causes loss of LRC primarily through proliferation. We conclude that LRC are more sensitive to some proliferative stimuli than others and that changes in lineage can occur with or without recruitment of LRC into cycle.
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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 [17]
BrdU label persists in quiescent bulge cells for more than six months.
“consistent with previous observations that BrdU label persists in quiescent bulge cells for more than six months17.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [17]
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- Authors
- Braun, K. M., Niemann, C., Jensen, U. B., Sundberg, J. P., Silva-Vargas, V., & Watt, F. M.
- Affiliations
- Cancer Research UK (GB)
- Aarhus University (DK)
- Jackson Laboratory (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-11-01
- Volume
- 130
- Issue
- 21
- Pages
- 5241-5255
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2063886817
- Cited by
- 425
- References
- 65
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 16 · 2019: 12 · 2018: 14 · 2017: 18 · 2016: 18 · 2015: 20 · 2014: 29 · 2013: 28 · 2012: 22
- FWCI
- 25.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Center for Research Resources (RR 173)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- epidermal stem cells, label-retaining cells, hair follicle stem cells, interfollicular epidermis, sebaceous glands, keratin 15, alpha6beta4 integrin, phorbol ester, c-Myc, LEF1, β-catenin signaling, transdifferentiation, stem cell proliferation, lineage commitment, mouse epidermis
- MeSH terms
- Epidermal Cells, Animals, Bromodeoxyuridine, Cell Division, DNA-Binding Proteins, Epidermis, Hair, Mice, Transgenic, Staining and Labeling, Stem Cells, Transcription Factors, Biomarkers, Proto-Oncogene Proteins c-myc, Histocytological Preparation Techniques, Cell Lineage, Mice, Lymphoid Enhancer-Binding Factor 1
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