A newly identified gene Ahed plays essential roles in murine haematopoiesis

Ritsuko Nakai, Takafumi Yokota (), Masahiro Tokunaga, Mikiro Takaishi, Tomomasa Yokomizo, Takao Sudo, Henyun Shi, Yoshiaki Yasumizu, Daisuke Okuzaki, Chikara Kokubu, Sachiyo Tanaka, Katsuyoshi Takaoka, Ayako Yamanishi, Junko Yoshida, Hitomi Watanabe, Gen Kondoh, Kyoji Horie, Naoki Hosen, Shigetoshi Sano and Junji Takeda ()
Additional contact information
Ritsuko Nakai: Osaka University
Takafumi Yokota: Osaka University
Masahiro Tokunaga: Suita Municipal Hospital
Mikiro Takaishi: Kochi University
Tomomasa Yokomizo: Tokyo Women’s Medical University
Takao Sudo: Osaka University
Henyun Shi: Osaka University
Yoshiaki Yasumizu: Osaka University
Daisuke Okuzaki: Osaka University
Chikara Kokubu: Osaka University
Sachiyo Tanaka: Osaka University
Katsuyoshi Takaoka: Osaka University
Ayako Yamanishi: Osaka University
Junko Yoshida: Osaka University
Hitomi Watanabe: Kyoto University
Gen Kondoh: Kyoto University
Kyoji Horie: Osaka University
Naoki Hosen: Osaka University
Shigetoshi Sano: Kochi University
Junji Takeda: Osaka University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49252-7

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