Journal
CELL STEM CELL
Volume 23, Issue 5, Pages 677-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2018.09.005
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Funding
- New York Stem Cell Foundation
- Edward Mallinckrodt, Jr. Foundation
- Glenn Foundation for Medical Research
- HHMI scholar award
- National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS) NIH grants [2R01AR063663-06A1, 1R01AR072668-01, 5R01AR067755-02]
- NIH Predoctoral Program in Cellular and Molecular Biology [T32GM007223]
- Burroughs Wellcome Fund
- Canadian Institutes of Health Research postdoctoral fellowship
- [28-908]
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Maintenance of adult tissues depends on sustained activity of resident stem cell populations, but the mechanisms that regulate stem cell self-renewal during homeostasis remain largely unknown. Using an imaging and tracking approach that captures all epidermal stem cell activity in large regions of living mice, we show that self-renewal is locally coordinated with epidermal differentiation, with a lag time of 1 to 2 days. In both homeostasis and upon experimental perturbation, we find that differentiation of a single stem cell is followed by division of a direct neighbor, but not vice versa. Finally, we show that exit from the stem cell compartment is sufficient to drive neighboring stem cell self-renewal. Together, these findings establish that epidermal stem cell self-renewal is not the constitutive driver of homeostasis. Instead, it is precisely tuned to tissue demand and responds directly to neighbor cell differentiation.
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