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Discovery of a periosteal stem cell mediating intramembranous bone formation

Author

Listed:
  • Shawon Debnath

    (Weill Cornell Medicine)

  • Alisha R. Yallowitz

    (Weill Cornell Medicine)

  • Jason McCormick

    (Weill Cornell Medicine)

  • Sarfaraz Lalani

    (Weill Cornell Medicine)

  • Tuo Zhang

    (Weill Cornell Medicine)

  • Ren Xu

    (Weill Cornell Medicine)

  • Na Li

    (Weill Cornell Medicine)

  • Yifang Liu

    (Weill Cornell Medicine)

  • Yeon Suk Yang

    (University of Massachusetts Medical School)

  • Mark Eiseman

    (Weill Cornell Medicine)

  • Jae-Hyuck Shim

    (University of Massachusetts Medical School)

  • Meera Hameed

    (Memorial Sloan Kettering Cancer Center)

  • John H. Healey

    (Memorial Sloan Kettering Cancer Center)

  • Mathias P. Bostrom

    (Hospital for Special Surgery
    Hospital for Special Surgery)

  • Dan Avi Landau

    (Weill Cornell Medicine
    New York Genome Center)

  • Matthew B. Greenblatt

    (Weill Cornell Medicine)

Abstract

Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear1–5. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway4, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.

Suggested Citation

  • Shawon Debnath & Alisha R. Yallowitz & Jason McCormick & Sarfaraz Lalani & Tuo Zhang & Ren Xu & Na Li & Yifang Liu & Yeon Suk Yang & Mark Eiseman & Jae-Hyuck Shim & Meera Hameed & John H. Healey & Mat, 2018. "Discovery of a periosteal stem cell mediating intramembranous bone formation," Nature, Nature, vol. 562(7725), pages 133-139, October.
  • Handle: RePEc:nat:nature:v:562:y:2018:i:7725:d:10.1038_s41586-018-0554-8
    DOI: 10.1038/s41586-018-0554-8
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    Citations

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    Cited by:

    1. Yuki Matsushita & Angel Ka Yan Chu & Chiaki Tsutsumi-Arai & Shion Orikasa & Mizuki Nagata & Sunny Y. Wong & Joshua D. Welch & Wanida Ono & Noriaki Ono, 2022. "The fate of early perichondrial cells in developing bones," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Xianzhu Zhang & Wei Jiang & Chang Xie & Xinyu Wu & Qian Ren & Fei Wang & Xilin Shen & Yi Hong & Hongwei Wu & Youguo Liao & Yi Zhang & Renjie Liang & Wei Sun & Yuqing Gu & Tao Zhang & Yishan Chen & Wei, 2022. "Msx1+ stem cells recruited by bioactive tissue engineering graft for bone regeneration," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Zan Li & Baohong Shi & Na Li & Jun Sun & Xiangchen Zeng & Rui Huang & Seoyeon Bok & Xiaohui Chen & Jie Han & Alisha R. Yallowitz & Shawon Debnath & Michelle Cung & Zheng Ling & Chuan-Qi Zhong & Yixang, 2024. "Bone controls browning of white adipose tissue and protects from diet-induced obesity through Schnurri-3-regulated SLIT2 secretion," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Lijun Wang & Xiuling You & Dengfeng Ruan & Rui Shao & Hai-Qiang Dai & Weiliang Shen & Guo-Liang Xu & Wanlu Liu & Weiguo Zou, 2022. "TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. 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.
    6. 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.
    7. Greg Holmes & Ana S. Gonzalez-Reiche & Madrikha Saturne & Susan M. Motch Perrine & Xianxiao Zhou & Ana C. Borges & Bhavana Shewale & Joan T. Richtsmeier & Bin Zhang & Harm Bakel & Ethylin Wang Jabs, 2021. "Single-cell analysis identifies a key role for Hhip in murine coronal suture development," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    8. Madison L. Doolittle & Dominik Saul & Japneet Kaur & Jennifer L. Rowsey & Stephanie J. Vos & Kevin D. Pavelko & Joshua N. Farr & David G. Monroe & Sundeep Khosla, 2023. "Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. 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.
    10. 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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