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Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life

Author

Listed:
  • Kyriel M. Pineault

    (University of Wisconsin-Madison)

  • Jane Y. Song

    (University of Michigan)

  • Kenneth M. Kozloff

    (University of Michigan)

  • Daniel Lucas

    (Cincinnati Children’s Medical Center)

  • Deneen M. Wellik

    (University of Wisconsin-Madison)

Abstract

Multipotent mesenchymal stromal cells (MSCs) are required for skeletal formation, maintenance, and repair throughout life; however, current models posit that postnatally arising long-lived adult MSCs replace transient embryonic progenitor populations. We previously reported exclusive expression and function of the embryonic patterning transcription factor, Hoxa11, in adult skeletal progenitor-enriched MSCs. Here, using a newly generated Hoxa11-CreERT2 lineage-tracing system, we show Hoxa11-lineage marked cells give rise to all skeletal lineages throughout the life of the animal and persist as MSCs. Hoxa11 lineage-positive cells give rise to previously described progenitor-enriched MSC populations marked by LepR-Cre and Osx-CreER, placing them upstream of these populations. Our studies establish that Hox-expressing cells are skeletal stem cells that arise from the earliest stages of skeletal development and self-renew throughout the life of the animal.

Suggested Citation

  • Kyriel M. Pineault & Jane Y. Song & Kenneth M. Kozloff & Daniel Lucas & Deneen M. Wellik, 2019. "Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11100-4
    DOI: 10.1038/s41467-019-11100-4
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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. 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.
    4. 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.
    5. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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