A newly identified gene Ahed plays essential roles in murine haematopoiesis.
Ritsuko NakaiTakafumi YokotaMasahiro TokunagaMikiro TakaishiTomomasa YokomizoTakao SudoHenyun ShiYoshiaki YasumizuDaisuke OkuzakiChikara KokubuSachiyo TanakaKatsuyoshi TakaokaAyako YamanishiJunko YoshidaHitomi WatanabeGen KondohKyoji HorieNaoki HosenShigetoshi SanoJunji TakedaPublished in: Nature communications (2024)
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.
Keyphrases
- genome wide
- genome wide identification
- copy number
- induced apoptosis
- dna methylation
- genome wide analysis
- cell cycle arrest
- embryonic stem cells
- transcription factor
- wild type
- pregnant women
- randomized controlled trial
- stem cells
- systematic review
- oxidative stress
- cell proliferation
- signaling pathway
- type diabetes
- adipose tissue
- cell death
- bone marrow
- artificial intelligence
- skeletal muscle
- big data
- breast cancer cells
- squamous cell