A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30814736
DOI
10.1038/s41586-019-0989-6
PII: 10.1038/s41586-019-0989-6
Knihovny.cz E-resources
- MeSH
- Cell Self Renewal MeSH
- Clone Cells cytology metabolism MeSH
- Chondrocytes cytology MeSH
- Cartilage cytology MeSH
- Mechanistic Target of Rapamycin Complex 1 metabolism MeSH
- Mice MeSH
- Stem Cell Niche physiology MeSH
- Growth Plate cytology metabolism MeSH
- Aging MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Mechanistic Target of Rapamycin Complex 1 MeSH
Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification1. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth1,2, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
Center for Hematology and Regenerative Medicine Karolinska Institutet Huddinge Sweden
Department of Neuroscience Karolinska Institutet Stockholm Sweden
Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
References provided by Crossref.org
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