학술논문

A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage
Document Type
article
Source
Nature Cell Biology. 21(9)
Subject
Biological Sciences
Genetics
Stem Cell Research - Nonembryonic - Non-Human
Regenerative Medicine
Stem Cell Research
1.1 Normal biological development and functioning
Underpinning research
Ameloblasts
Animals
Cell Differentiation
Cell Division
Cell Proliferation
Ectoderm
Epithelial Cells
Incisor
Mice
Transgenic
Signal Transduction
Stem Cells
Medical and Health Sciences
Developmental Biology
Biochemistry and cell biology
Language
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.