A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage.
- Sharir A Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Marangoni P Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Zilionis R Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
- Wan M Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Wald T Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Hu JK Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Kawaguchi K Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
- Castillo-Azofeifa D Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
- Epstein L Bioinformatics and Computational Biology Program, University of Idaho, Moscow, ID, USA.
- Harrington K Bioinformatics and Computational Biology Program, University of Idaho, Moscow, ID, USA.
- Pagella P Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland.
- Mitsiadis T Orofacial Development and Regeneration, Institute of Oral Biology, Centre of Dental Medicine, University of Zurich, Zurich, Switzerland.
- Siebel CW Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
- Klein AM Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Allon_Klein@hms.harvard.edu.
- Klein OD Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA. Ophir.Klein@ucsf.edu.
- 2019-09-05
Published in:
- Nature cell biology. - 2019
Ameloblasts
Animals
Cell Differentiation
Cell Division
Cell Proliferation
Ectoderm
Epithelial Cells
Incisor
Mice, Transgenic
Signal Transduction
Stem Cells
English
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.
- Language
-
- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/s41556-019-0378-2
- PMID 31481792
- Persistent URL
- https://sonar.ch/global/documents/260848
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