Hemogenic endothelium specification and hematopoietic stem cell maintenance employ distinct Scl isoforms
Hemogenic endothelium specification and hematopoietic stem cell maintenance employ distinct Scl isoforms
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造血内皮规范和造血干细胞维持采用不同的 Scl 亚型
DOI：
10.1242/dev.097071
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发表时间：
2013-10
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：
Lan, Yahui;Yan, Bo;Zhang, Wenqing;Wen, Zilong
最近的研究表明，新生造血干细胞(HSCs)直接来源于腹主动脉内皮细胞(VAE)，通过内皮细胞向造血细胞转化(EHT)。然而，EHT是从VAE的随机亚群还是预定亚群开始的，以及这一过程背后的分子机制仍不清楚。我们先前报道，不同的斑马鱼干细胞白血病(SCL)亚型是形成腹主动脉腹壁HSC所必需的不同亚型。然而，这些异构体影响HSC发育的确切阶段还没有定义。在此，通过对转scl异构体报告基因斑马鱼的体内时移成像，我们发现在高血压之前，scl-β在血源性内皮细胞中有选择性地表达，而scl-α在新生的肝星状细胞中表达，当它们从血管内皮细胞中排出时。根据它们的表达，功能丧失研究结合体内成像分析表明，SCL-β较早作用于指定的血源性内皮，后者后来被RUNX1转化为造血干细胞。我们的结果还揭示了SCL-α在维持主动脉-性腺-中肾中新生的HSCs方面的先前意想不到的作用。因此，我们的数据表明，SCL-β预设的一个明确的血源性内皮细胞群支持造血干细胞的确定性出现，并揭示了SCL亚型调控造血干细胞发育的细胞机制。
Recent studies have shown that nascent hematopoietic stem cells (HSCs) derive directly from the ventral aortic endothelium (VAE) via endothelial to hematopoietic transition (EHT). However, whether EHT initiates from a random or predetermined subpopulation of VAE, as well as the molecular mechanism underlying this process, remain unclear. We previously reported that different zebrafish stem cell leukemia (scl) isoforms are differentially required for HSC formation in the ventral wall of the dorsal aorta. However, the exact stage at which these isoforms impact HSC development was not defined. Here, using in vivo time-lapse imaging of scl isoform-specific reporter transgenic zebrafish lines, we show that prior to EHT scl-β is selectively expressed in hemogenic endothelial cells, a unique subset of VAE cells possessing hemogenic potential, whereas scl-α is expressed later in nascent HSCs as they egress from VAE cells. In accordance with their expression, loss-of-function studies coupled with in vivo imaging analysis reveal that scl-β acts earlier to specify hemogenic endothelium, which is later transformed by runx1 into HSCs. Our results also reveal a previously unexpected role of scl-α in maintaining newly born HSCs in the aorta-gonads-mesonephros. Thus, our data suggest that a defined hemogenic endothelial population preset by scl-β supports the deterministic emergence of HSCs, and unravel the cellular mechanisms by which scl isoforms regulate HSC development.
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影响因子：
20.3
作者：
Yiyue Zhang;H. Jin;Li Li-Li;F. Qin;Zilong Wen
通讯作者：
Yiyue Zhang;H. Jin;Li Li-Li;F. Qin;Zilong Wen
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
64.5
作者：
Porcher, C;Swat, W;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
2.7
作者：
Dooley, KA;Davidson, AJ;Zon, LI
通讯作者：
Zon, LI
影响因子：
4.6
作者：
C. Porcher;Eric C. Liao;Y. Fujiwara;Leonard I. Zon;Stuart H. Orkin
通讯作者：
C. Porcher;Eric C. Liao;Y. Fujiwara;Leonard I. Zon;Stuart H. Orkin