Header

UZH-Logo

Maintenance Infos

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


Sharir, Amnon; Marangoni, Pauline; Zilionis, Rapolas; Wan, Mian; Wald, Tomas; Hu, Jimmy K; Kawaguchi, Kyogo; Castillo-Azofeifa, David; Epstein, Leo; Harrington, Kyle; Pagella, Pierfrancesco; Mitsiadis, Thimios; Siebel, Christian W; Klein, Allon M; Klein, Ophir D (2019). A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage. Nature Cell Biology, 21(9):1102-1112.

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.

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.

Statistics

Citations

Dimensions.ai Metrics
21 citations in Web of Science®
20 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 13 Feb 2020
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Institute of Oral Biology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Cell Biology
Language:English
Date:September 2019
Deposited On:13 Feb 2020 16:28
Last Modified:29 Jul 2020 12:41
Publisher:Nature Publishing Group
ISSN:1465-7392
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41556-019-0378-2
PubMed ID:31481792

Download

Closed Access: Download allowed only for UZH members