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

First Author  Sharir A Year  2019
Journal  Nat Cell Biol Volume  21
Issue  9 Pages  1102-1112
PubMed ID  31481792 Mgi Jnum  J:282936
Mgi Id  MGI:6384178 Doi  10.1038/s41556-019-0378-2
Citation  Sharir A, et al. (2019) A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage. Nat Cell Biol 21(9):1102-1112
abstractText  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.
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