A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plateCzech Acad Sci, Inst Expt Med, Dept Dev Biol, Prague, Czech Republic..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden..
Karolinska Inst, Ctr Hematol & Regenerat Med, Huddinge, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Russian Acad Sci, Far Eastern Branch, Natl Sci Ctr Marine Biol, Vladivostok, Russia..
Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
KTH, Centres, Science for Life Laboratory, SciLifeLab.
SUNY Stony Brook, Ctr Dev Genet, Stony Brook, NY 11794 USA.;SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
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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-+
National Category
Cell and Molecular Biology
Identifiers
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
Note
QC 20190509
2019-05-092019-05-092022-06-26Bibliographically approved