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Nat Cell Biol. 2019 Sep;21(9):1102-1112. doi: 10.1038/s41556-019-0378-2. Epub 2019 Sep 2.

A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage.

Author information

1
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
2
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
3
Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
4
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
5
Universal Biology Institute, The University of Tokyo, Tokyo, Japan.
6
Bioinformatics and Computational Biology Program, University of Idaho, Moscow, ID, USA.
7
Virtual Technology and Design, University of Idaho, Moscow, ID, USA.
8
Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland.
9
Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
10
Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Allon_Klein@hms.harvard.edu.
11
Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA. Ophir.Klein@ucsf.edu.
12
Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, CA, USA. Ophir.Klein@ucsf.edu.

Abstract

The classical model of tissue renewal posits that small numbers of quiescent stem cells (SCs) give rise to proliferating transit-amplifying cells before terminal differentiation. However, many organs house pools of SCs with proliferative and differentiation potentials that diverge from this template. Resolving SC identity and organization is therefore central to understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNA-seq), mouse genetics and tissue injury approaches, we uncover cellular hierarchies and mechanisms that underlie the maintenance and repair of the continuously growing mouse incisor. Our results reveal that, during homeostasis, a group of actively cycling epithelial progenitors generates enamel-producing ameloblasts and adjacent layers of non-ameloblast cells. After injury, tissue repair was achieved through transient increases in progenitor-cell proliferation and through direct conversion of Notch1-expressing cells to ameloblasts. We elucidate epithelial SC identity, position and function, providing a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage.

PMID:
31481792
DOI:
10.1038/s41556-019-0378-2
[Indexed for MEDLINE]

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