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Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells

Author

Listed:
  • Yoshiki Omatsu

    (Osaka University
    Osaka University
    Osaka University)

  • Shota Aiba

    (Osaka University
    Osaka University
    Osaka University)

  • Tomonori Maeta

    (Osaka University
    Osaka University
    Osaka University)

  • Kei Higaki

    (Osaka University
    Osaka University
    Osaka University)

  • Kazunari Aoki

    (Kyoto University)

  • Hitomi Watanabe

    (Kyoto University)

  • Gen Kondoh

    (Kyoto University)

  • Riko Nishimura

    (Osaka University)

  • Shu Takeda

    (Endocrinology Division, Toranomon Hospital)

  • Ung-il Chung

    (The University of Tokyo)

  • Takashi Nagasawa

    (Osaka University
    Osaka University
    Osaka University)

Abstract

In bone marrow, special microenvironments, known as niches, are essential for the maintenance of hematopoietic stem cells (HSCs). A population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-expressing cells are the major cellular component of HSC niches. The molecular regulation of HSC niche properties is not fully understood. The role of Runx transcription factors, Runx1 and Runx2 in HSC cellular niches remains unclear. Here we show that Runx1 is predominantly expressed in CAR cells and that mice lacking both Runx1 and Runx2 in CAR cells display an increase in fibrosis and bone formation with markedly reduced hematopoietic stem and progenitor cells in bone marrow. In vitro, Runx1 is induced by the transcription factor Foxc1 and decreases fibrotic gene expression in CAR cells. Thus, HSC cellular niches require Runx1 or Runx2 to prevent their fibrotic conversion and maintain HSCs and hematopoiesis in adults.

Suggested Citation

  • Yoshiki Omatsu & Shota Aiba & Tomonori Maeta & Kei Higaki & Kazunari Aoki & Hitomi Watanabe & Gen Kondoh & Riko Nishimura & Shu Takeda & Ung-il Chung & Takashi Nagasawa, 2022. "Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30266-y
    DOI: 10.1038/s41467-022-30266-y
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    References listed on IDEAS

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    1. 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.

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