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Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

Author

Listed:
  • Taichi Nakatani

    (Osaka University
    Osaka University
    Osaka University)

  • Tatsuki Sugiyama

    (Osaka University
    Osaka University
    Osaka University)

  • Yoshiki Omatsu

    (Osaka University
    Osaka University
    Osaka University)

  • Hitomi Watanabe

    (Kyoto University)

  • Gen Kondoh

    (Kyoto University)

  • Takashi Nagasawa

    (Osaka University
    Osaka University
    Osaka University)

Abstract

Lympho-hematopoiesis is regulated by cytokines; however, it remains unclear how cytokines regulate hematopoietic stem cells (HSCs) to induce production of lymphoid progenitors. Here, we show that in mice whose CXC chemokine ligand 12 (CXCL12) is deleted from half HSC niche cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, HSCs migrate from CXCL12-deficient niches to CXCL12-intact niches. In mice whose CXCL12 is deleted from all Ebf3+/leptin receptor (LepR)+ CAR cells, HSCs are markedly reduced and their ability to generate B cell progenitors is reduced compared with that to generate myeloid progenitors even when transplanted into wild-type mice. Additionally, CXCL12 enables the maintenance of B lineage repopulating ability of HSCs in vitro. These results demonstrate that CAR cell-derived CXCL12 attracts HSCs to CAR cells within bone marrow and plays a critical role in the maintenance of HSCs, especially lymphoid-biased or balanced HSCs. This study suggests an additional mechanism by which cytokines act on HSCs to produce B cells.

Suggested Citation

  • Taichi Nakatani & Tatsuki Sugiyama & Yoshiki Omatsu & Hitomi Watanabe & Gen Kondoh & Takashi Nagasawa, 2023. "Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42047-2
    DOI: 10.1038/s41467-023-42047-2
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    References listed on IDEAS

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