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A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..ORCID iD: 0000-0003-2142-1798
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden..ORCID iD: 0000-0003-4505-9068
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2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 567, no 7747, p. 234-+Article in journal (Refereed) Published
Abstract [en]

Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification 1 . 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 growth 1,2 , 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 celldivision. 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 567, no 7747, p. 234-+
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Cell and Molecular Biology
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URN: urn:nbn:se:kth:diva-251299DOI: 10.1038/s41586-019-0989-6ISI: 000461126600041PubMedID: 30814736Scopus ID: 2-s2.0-85062621397OAI: oai:DiVA.org:kth-251299DiVA, id: diva2:1314673
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QC 20190509

Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-09Bibliographically approved

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Mollbrink, AnnelieLundeberg, Joakim

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