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.
摘要:
造血的发展涉及众多基因的协调作用,其中一些与血液恶性肿瘤有关。然而,许多基因的生物学功能仍然难以捉摸,未知的功能基因可能仍然有待发现。这里,我们报道了一个以前没有特征的造血基因,通过筛选突变的胚胎干细胞鉴定。基因,“造血发育减弱(Ahed)”,编码核蛋白。Ahed的条件敲除(cKO)导致贫血,从胚胎第14.5天开始,导致产前死亡.移植实验表明,Ahed缺陷的造血细胞无法在体内重建造血。采用他莫昔芬诱导的cKO模型,我们进一步揭示了Ahed缺失会损害成年小鼠造血细胞的内在能力。Ahed缺失影响各种途径,和已发表的数据库提供了Ahed体细胞突变的癌症患者。总的来说,我们的发现强调了Ahed在终身造血中的基本作用,暗示其与恶性肿瘤有关。