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

Item Type:	Article
Title:	A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage
Creators Name:	Sharir, A. and Marangoni, P. and Zilionis, R. and Wan, M. and Wald, T. and Hu, J.K. and Kawaguchi, K. and Castillo-Azofeifa, D. and Epstein, L. and Harrington, K. and Pagella, P. and Mitsiadis, T. and Siebel, C.W. and Klein, A.M. and Klein, O.D.
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.
Keywords:	Ameloblasts, Cell Differentiation, Cell Division, Cell Proliferation, Ectoderm, Epithelial Cells, Incisor, Signal Transduction, Stem Cells, Transgenic Mice, Animals, Mice
Source:	Nature Cell Biology
ISSN:	1465-7392
Publisher:	Nature Publishing Group
Volume:	21
Number:	9
Page Range:	1102-1112
Date:	September 2019
Official Publication:	https://doi.org/10.1038/s41556-019-0378-2
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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