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

Amnon Sharir, Pauline Marangoni, Rapolas Zilionis, Mian Wan, Tomas Wald, Jimmy K. Hu, Kyogo Kawaguchi, David Castillo-Azofeifa, Leo Epstein, Kyle Harrington, Pierfrancesco Pagella, Thimios Mitsiadis, Christian W. Siebel, Allon M. Klein, Ophir D. Klein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1102-1112
Number of pages11
JournalNature Cell Biology
Volume21
Issue number9
DOIs
StatePublished - 1 Sep 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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