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

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature cell biology 2019-09, Vol.21 (9), p.1102-1112
Hauptverfasser: 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.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. Sharir et al. overhaul the classical model and show that proliferating inner-enamel progenitors generate all epithelial lineages and their Notch1-expressing progeny convert into ameloblasts after injury.
ISSN:1465-7392
1476-4679
DOI:10.1038/s41556-019-0378-2