Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages.
Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages.
复制标题
DOI：
10.1038/ncb3161
复制
发表时间：
2015-05
影响因子：
21.3
通讯作者：
Keller G
中科院分区：
文献类型：
--
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
从人类多能干细胞（hPSCs）生成造血干细胞（HSCs）将取决于对胚胎造血作用的精确重现。在早期胚胎中，造血干细胞从生血内皮（HE）发育而来，并通过一种名为内皮细胞向造血细胞转变（EHT）的过程以依赖Notch的方式被特化。由于生血内皮与动脉相关，人们假定它代表动脉血管内皮（VE）的一个亚群。在此，我们在克隆水平上证明，源自人类多能干细胞的生血内皮和血管内皮代表不同的谱系。生血内皮局限于第8天拟胚体（EBs）的CD34⁺CD73⁻CD184⁻组分，并且它经历依赖Notch的内皮细胞向造血细胞转变，以产生具有多向分化潜能的RUNX1C⁺细胞。相比之下，动脉和静脉血管内皮祖细胞分别分离到CD34⁺CD73⁽中⁾CD184⁺和CD34⁺CD73⁽高⁾CD184⁻组分。总之，这些发现确定生血内皮不同于血管内皮，并为定义调控它们特化为功能性造血干细胞的信号通路提供了一个平台。
The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) will depend on the accurate recapitulation of embryonic haematopoiesis. In the early embryo, HSCs develop from the haemogenic endothelium (HE) and are specified in a Notch-dependent manner through a process named endothelial-to-haematopoietic transition (EHT). As HE is associated with arteries, it is assumed that it represents a subpopulation of arterial vascular endothelium (VE). Here we demonstrate at a clonal level that hPSC-derived HE and VE represent separate lineages. HE is restricted to the CD34+CD73−CD184− fraction of day 8 embryoid bodies (EBs) and it undergoes a NOTCH-dependent EHT to generate RUNX1C+ cells with multilineage potential. Arterial and venous VE progenitors, by contrast, segregate to the CD34+CD73medCD184+ and CD34+CD73hiCD184− fractions, respectively. Together, these findings identify HE as distinct from VE and provide a platform for defining the signalling pathways that regulate their specification to functional HSCs.