State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.
Blood. 2011 Oct 13;118(15):4093-101. doi: 10.1182/blood-2011-03-342501. Epub 2011 Aug 19.
The establishment of the HSC pool in vertebrates depends not only on the formation and the propagation of these stem cells but also on their proper trafficking among the defined hematopoietic organs. However, the physiologic mechanisms that regulate HSC mobilization remain elusive. Through analysis of the zebrafish cmyb mutant cmyb(hkz3), we show that the suppression of cMyb function abrogates larval and adult hematopoiesis, with concomitant accumulation of hematopoietic stem/progenitor cells (HSPCs) in their birthplace, the ventral wall of the dorsal aorta (VDA). Cell tracking and time-lapse recording reveal that the accumulation of HSPCs in cmyb(hkz3) mutants is caused by the impairment of HSPC egression from the VDA. Further analysis demonstrates that the HSPC migratory defects in cmyb(hkz3) mutants are at least partly because of adversely elevated levels of chemokine stromal cell-derived factor 1a (Sdf1a). Our study reveals that cMyb plays a hitherto unidentified role in dictating physiologic HSPC migration by modulating Sdf1a signaling.
脊椎动物中 HSC 库的建立不仅取决于这些干细胞的形成和增殖，还取决于它们在特定造血器官之间的适当运输。然而，调节 HSC 动员的生理机制仍不清楚。通过对斑马鱼 cmyb 突变体 cmyb(hkz3)的分析，我们表明抑制 cMyb 功能会破坏幼虫和成体造血，并伴随着造血干细胞/祖细胞 (HSPC) 在其发源地，背主动脉 (VDA) 的腹侧壁的积累。细胞追踪和延时记录显示，cmyb(hkz3)突变体中 HSPC 的积累是由于 HSPC 从 VDA 中逸出受损所致。进一步的分析表明，cmyb(hkz3)突变体中的 HSPC 迁移缺陷至少部分是由于趋化因子基质细胞衍生因子 1a (Sdf1a)的水平升高所致。我们的研究表明，cMyb 通过调节 Sdf1a 信号转导，在决定生理 HSPC 迁移方面发挥了迄今为止尚未确定的作用。
