WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis.
WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis.
复制标题
胎儿肝血管生态位的Wnt5a支持人类胎儿肝造血。
DOI：
10.1186/s13287-021-02380-z
复制
发表时间：
2021-06-05
影响因子：
7.5
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Choi YJ;Heck AM;Hayes BJ;Lih D;Rayner SG;Hadland B;Zheng Y
人胎肝是产前造血的重要器官，对它的研究有助于了解在胎儿发育过程中调控造血干细胞和祖细胞（HSPCs）命运的小生境信号。在这里，我们证明了人胎肝内皮细胞独特地支持多谱系HSPCs的成熟和扩增。具体而言，与来自其他器官的EC共培养相比，胎肝来源的未成熟CD 43 + CD 45 −造血细胞与人胎肝内皮细胞（EC）共培养导致体外产生的表型CD 45 + CD 34 + HSPC和多系集落形成祖细胞的数量显著增加。我们通过EC内的功能获得和丧失研究进一步确定了EC衍生的WNT 5A在此过程中的支持作用。我们的研究强调了器官特异性内皮生态位在支持造血发育中的重要性，并提供了对可能促进HSPC体外扩增用于临床应用的信号的新见解。在线版本包含补充材料，可通过10.1186/s13287-021-02380-z获得。
The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45− hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications. The online version contains supplementary material available at 10.1186/s13287-021-02380-z.