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A newly identified gene Ahed plays essential roles in murine haematopoiesis

Author

Listed:
  • Ritsuko Nakai

    (Osaka University)

  • Takafumi Yokota

    (Osaka University
    Osaka International Cancer Institute)

  • Masahiro Tokunaga

    (Suita Municipal Hospital
    Osaka University)

  • Mikiro Takaishi

    (Kochi University)

  • Tomomasa Yokomizo

    (Tokyo Women’s Medical University)

  • Takao Sudo

    (Osaka University
    National Hospital Organisation Osaka National Hospital)

  • Henyun Shi

    (Osaka University)

  • Yoshiaki Yasumizu

    (Osaka University
    Osaka University)

  • Daisuke Okuzaki

    (Osaka University
    Osaka University)

  • Chikara Kokubu

    (Osaka University)

  • Sachiyo Tanaka

    (Osaka University)

  • Katsuyoshi Takaoka

    (Osaka University)

  • Ayako Yamanishi

    (Osaka University)

  • Junko Yoshida

    (Osaka University
    Nara Medical University)

  • Hitomi Watanabe

    (Kyoto University)

  • Gen Kondoh

    (Kyoto University)

  • Kyoji Horie

    (Osaka University
    Nara Medical University)

  • Naoki Hosen

    (Osaka University
    Osaka University
    Osaka University)

  • Shigetoshi Sano

    (Kochi University)

  • Junji Takeda

    (Osaka University)

Abstract

The development of haematopoiesis involves the coordinated action of numerous genes, some of which are implicated in haematological malignancies. However, the biological function of many genes remains elusive and unknown functional genes are likely to remain to be uncovered. Here, we report a previously uncharacterised gene in haematopoiesis, identified by screening mutant embryonic stem cells. The gene, ‘attenuated haematopoietic development (Ahed)’, encodes a nuclear protein. Conditional knockout (cKO) of Ahed results in anaemia from embryonic day 14.5 onward, leading to prenatal demise. Transplantation experiments demonstrate the incapacity of Ahed-deficient haematopoietic cells to reconstitute haematopoiesis in vivo. Employing a tamoxifen-inducible cKO model, we further reveal that Ahed deletion impairs the intrinsic capacity of haematopoietic cells in adult mice. Ahed deletion affects various pathways, and published databases present cancer patients with somatic mutations in Ahed. Collectively, our findings underscore the fundamental roles of Ahed in lifelong haematopoiesis, implicating its association with malignancies.

Suggested Citation

  • Ritsuko Nakai & Takafumi Yokota & Masahiro Tokunaga & Mikiro Takaishi & Tomomasa Yokomizo & Takao Sudo & Henyun Shi & Yoshiaki Yasumizu & Daisuke Okuzaki & Chikara Kokubu & Sachiyo Tanaka & Katsuyoshi, 2024. "A newly identified gene Ahed plays essential roles in murine haematopoiesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49252-7
    DOI: 10.1038/s41467-024-49252-7
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