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Cell Stem Cell. 2018 Nov 1;23(5):677-686.e4. doi: 10.1016/j.stem.2018.09.005. Epub 2018 Sep 27.

Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation.

Author information

1
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
2
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Universal Biology Institute, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
3
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: katherine.cockburn@yale.edu.
4
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: allon_klein@hms.harvard.edu.
5
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Departments of Cell Biology and Dermatology, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: valentina.greco@yale.edu.

Abstract

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.

KEYWORDS:

epidermis; fate coordination; homeostasis; intravital imaging; skin; stem cells

PMID:
30269903
PMCID:
PMC6214709
[Available on 2019-11-01]
DOI:
10.1016/j.stem.2018.09.005

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