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

Author

Listed:
  • Phillip T. Newton

    (Karolinska Institutet
    Karolinska University Hospital)

  • 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
    Sechenov First Moscow State Medical University)

  • Evgeny Ivashkin

    (Karolinska Institutet)

  • Simon Suter

    (Karolinska Institutet)

  • Vyacheslav Dyachuk

    (Karolinska Institutet
    Russian Academy of Sciences)

  • 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
    Medical University Vienna)

  • 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
    Medical University Vienna)

  • Lars Sävendahl

    (Karolinska University Hospital)

  • Andrei S. Chagin

    (Karolinska Institutet
    Sechenov First Moscow State Medical University)

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.

Suggested Citation

  • 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 , 2019. "A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate," Nature, Nature, vol. 567(7747), pages 234-238, March.
  • Handle: RePEc:nat:nature:v:567:y:2019:i:7747:d:10.1038_s41586-019-0989-6
    DOI: 10.1038/s41586-019-0989-6
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    Citations

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    Cited by:

    1. Aaron Warren & Ryan M. Porter & Olivia Reyes-Castro & Md Mohsin Ali & Adriana Marques-Carvalho & Ha-Neui Kim & Landon B. Gatrell & Ernestina Schipani & Intawat Nookaew & Charles A. O’Brien & Roy Morel, 2023. "The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Shanmugam Muruganandan & Rachel Pierce & Dian Astari Teguh & Rocio Fuente Perez & Nicole Bell & Brandon Nguyen & Katherine Hohl & Brian D. Snyder & Mark W. Grinstaff & Hannah Alberico & Dori Woods & Y, 2022. "A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Marketa Kaucka & Alberto Joven Araus & Marketa Tesarova & Joshua D. Currie & Johan Boström & Michaela Kavkova & Julian Petersen & Zeyu Yao & Anass Bouchnita & Andreas Hellander & Tomas Zikmund & Ahmed, 2022. "Altered developmental programs and oriented cell divisions lead to bulky bones during salamander limb regeneration," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Masayuki Tsukasaki & Noriko Komatsu & Takako Negishi-Koga & Nam Cong-Nhat Huynh & Ryunosuke Muro & Yutaro Ando & Yuka Seki & Asuka Terashima & Warunee Pluemsakunthai & Takeshi Nitta & Takashi Nakamura, 2022. "Periosteal stem cells control growth plate stem cells during postnatal skeletal growth," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Reza Mirzazadeh & Zaneta Andrusivova & Ludvig Larsson & Phillip T. Newton & Leire Alonso Galicia & Xesús M. Abalo & Mahtab Avijgan & Linda Kvastad & Alexandre Denadai-Souza & Nathalie Stakenborg & Ale, 2023. "Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Cheng-Hai Zhang & Yao Gao & Han-Hwa Hung & Zhu Zhuo & Alan J. Grodzinsky & Andrew B. Lassar, 2022. "Creb5 coordinates synovial joint formation with the genesis of articular cartilage," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Chee Ho H’ng & Shanika L. Amarasinghe & Boya Zhang & Hojin Chang & Xinli Qu & David R. Powell & Alberto Rosello-Diez, 2024. "Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Yuki Matsushita & Jialin Liu & Angel Ka Yan Chu & Chiaki Tsutsumi-Arai & Mizuki Nagata & Yuki Arai & Wanida Ono & Kouhei Yamamoto & Thomas L. Saunders & Joshua D. Welch & Noriaki Ono, 2023. "Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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