Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Sci China Life Sci. 2021 Dec;64(12):2186-2201. doi: 10.1007/s11427-020-1878-8. Epub 2021 Mar 16.
Hematopoietic stem and progenitor cells (HSPCs) are able to self-renew and can give rise to all blood lineages throughout their lifetime, yet the mechanisms regulating HSPC development have yet to be discovered. In this study, we characterized a hematopoiesis defective zebrafish mutant line named smu07, which was obtained from our previous forward genetic screening, and found the HSPC expansion deficiency in the mutant. Positional cloning identified that slc20a1b, which encodes a sodium phosphate cotransporter, contributed to the smu07 blood phenotype. Further analysis demonstrated that mutation of slc20a1b affects HSPC expansion through cell cycle arrest at G2/M phases in a cell-autonomous manner. Our study shows that slc20a1b is a vital regulator for HSPC proliferation in zebrafish early hematopoiesis and provides valuable insights into HSPC development.
造血干细胞和祖细胞 (HSPCs) 能够自我更新，并在其整个生命周期中产生所有的血液谱系，但调节 HSPC 发育的机制尚未被发现。在这项研究中，我们对一种名为 smu07 的造血缺陷斑马鱼突变系进行了特征描述，该突变系是我们之前通过正向遗传筛选获得的，并且在突变体中发现了 HSPC 扩增缺陷。定位克隆鉴定出 slc20a1b，它编码一种磷酸钠共转运体，导致了 smu07 的血液表型。进一步的分析表明， slc20a1b 的突变以细胞自主的方式通过 G2/M 期的细胞周期阻滞影响 HSPC 的扩增。我们的研究表明， slc20a1b 是斑马鱼早期造血中 HSPC 增殖的重要调节因子，并为 HSPC 发育提供了有价值的见解。
