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The aging skin microenvironment dictates stem cell behavior.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Mar 10; Vol. 117 (10), pp. 5339-5350. Date of Electronic Publication: 2020 Feb 24. - Publication Year :
- 2020
-
Abstract
- Aging manifests with architectural alteration and functional decline of multiple organs throughout an organism. In mammals, aged skin is accompanied by a marked reduction in hair cycling and appearance of bald patches, leading researchers to propose that hair follicle stem cells (HFSCs) are either lost, differentiate, or change to an epidermal fate during aging. Here, we employed single-cell RNA-sequencing to interrogate aging-related changes in the HFSCs. Surprisingly, although numbers declined, aging HFSCs were present, maintained their identity, and showed no overt signs of shifting to an epidermal fate. However, they did exhibit prevalent transcriptional changes particularly in extracellular matrix genes, and this was accompanied by profound structural perturbations in the aging SC niche. Moreover, marked age-related changes occurred in many nonepithelial cell types, including resident immune cells, sensory neurons, and arrector pili muscles. Each of these SC niche components has been shown to influence HF regeneration. When we performed skin injuries that are known to mobilize young HFSCs to exit their niche and regenerate HFs, we discovered that aged skin is defective at doing so. Interestingly, however, in transplantation assays in vivo, aged HFSCs regenerated HFs when supported with young dermis, while young HFSCs failed to regenerate HFs when combined with aged dermis. Together, our findings highlight the importance of SC:niche interactions and favor a model where youthfulness of the niche microenvironment plays a dominant role in dictating the properties of its SCs and tissue health and fitness.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Animals
Dermis physiology
Epidermal Cells physiology
Epidermis metabolism
Mice
Mice, Inbred C57BL
Muscles physiology
Re-Epithelialization
Regeneration genetics
Sensory Receptor Cells physiology
Skin Aging genetics
Stem Cell Niche genetics
Stem Cell Transplantation
Transcriptome
Wound Healing genetics
Wound Healing physiology
Hair Follicle physiology
Regeneration physiology
Skin Aging physiology
Stem Cell Niche physiology
Stem Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32094197
- Full Text :
- https://doi.org/10.1073/pnas.1901720117