SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish
SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish
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SUMO1 激活酶亚基 1 对于斑马鱼造血干/祖细胞的生存至关重要
DOI：
10.1242/dev.081869
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发表时间：
2012-12-01
期刊：
影响因子：
4.6
通讯作者：
Wen, Zilong
中科院分区：
文献类型：
--
作者：
Li, Xiuling;Lan, Yahui;Wen, Zilong
在脊椎动物中，造血干/祖细胞（HSPC）库的建立涉及这些细胞在连续发育的造血小生境中的动员。在斑马鱼中，HSPCs起源于背主动脉（VDA）的腹侧壁，相当于哺乳动物的腹主动脉-性腺-中肾（AGM）。HSPCs随后迁移到尾部造血组织（CHT）的短暂扩张和分化，在幼虫阶段，他们最终定殖肾脏，造血发生在成鱼。在这里，我们报告的分离和表征的斑马鱼突变体，tangohkz5，这表明明确的造血缺陷。在tangohkz5突变体中，HSPC通常在AGM中启动，随后定殖CHT。然而，由于HSPCs的加速凋亡和减少增殖，CHT中的确定性造血不能持续。定位克隆显示tangohkz5编码SUMO 1激活酶亚基1（Sae1）。嵌合体生成实验和生物化学分析表明，sae1是确定性造血所需的细胞自主性，并且tangohkz5突变产生截短的Sae1蛋白（Δ Sae1），导致系统性sumoylation减少。我们的研究结果表明，sae1是必不可少的维持HSPCs在胚胎造血在斑马鱼。
In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tangohkz5, which shows defects of definitive hematopoiesis. In tangohkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tangohkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive hematopoiesis and that the tangohkz5 mutation produces a truncated Sae1 protein (ΔSae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal hematopoiesis in zebrafish.