A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate

Phillip T. Newton (), Lei Li, Baoyi Zhou, Christoph Schweingruber, Maria Hovorakova, Meng Xie, Xiaoyan Sun, Lakshmi Sandhow, Artem V. Artemov, Evgeny Ivashkin, Simon Suter, Vyacheslav Dyachuk, Maha El Shahawy, Amel Gritli-Linde, Thibault Bouderlique, Julian Petersen, Annelie Mollbrink, Joakim Lundeberg, Grigori Enikolopov, Hong Qian, Kaj Fried, Maria Kasper, Eva Hedlund, Igor Adameyko, Lars Sävendahl and Andrei S. Chagin ()
Additional contact information
Phillip T. Newton: Karolinska Institutet
Lei Li: Karolinska Institutet
Baoyi Zhou: Karolinska Institutet
Christoph Schweingruber: Karolinska Institutet
Maria Hovorakova: The Czech Academy of Sciences
Meng Xie: Karolinska Institutet
Xiaoyan Sun: Karolinska Institutet
Lakshmi Sandhow: Karolinska Institutet
Artem V. Artemov: Karolinska Institutet
Evgeny Ivashkin: Karolinska Institutet
Simon Suter: Karolinska Institutet
Vyacheslav Dyachuk: Karolinska Institutet
Maha El Shahawy: Sahlgrenska Academy at the University of Gothenburg
Amel Gritli-Linde: Sahlgrenska Academy at the University of Gothenburg
Thibault Bouderlique: Karolinska Institutet
Julian Petersen: Karolinska Institutet
Annelie Mollbrink: KTH Royal Institute of Technology
Joakim Lundeberg: KTH Royal Institute of Technology
Grigori Enikolopov: Stony Brook University
Hong Qian: Karolinska Institutet
Kaj Fried: Karolinska Institutet
Maria Kasper: Karolinska Institutet
Eva Hedlund: Karolinska Institutet
Igor Adameyko: Karolinska Institutet
Lars Sävendahl: Karolinska University Hospital
Andrei S. Chagin: Karolinska Institutet

Nature, 2019, vol. 567, issue 7747, 234-238

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41586-019-0989-6

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