Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
INSERM U972, Hospital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807 Villejuif, France.
Stem Cell Reports. 2014 Oct 14;3(4):556-65. doi: 10.1016/j.stemcr.2014.08.009. Epub 2014 Sep 18.
Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs) that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1). Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.
器官发生需要胚胎血管丛的扩张，该血管丛通过称为血管生成的过程迁移到正在发育的器官中。中胚层祖细胞被认为来源于内皮细胞（ECs），这些细胞有助于胚胎血管发生和随后的器官血管生成。在这里，我们证明在肝脏的发育过程中，肝脏是内胚层的衍生物，一部分 ECs 是由表达 KDR（VEGFR2/FLK-1）的 FOXA2+内胚层来源的胎儿肝祖细胞产生的。使用人和小鼠胚胎干细胞模型，我们证明在肝分化培养中发育的 KDR+FOXA2+内胚层细胞可产生功能性 ECs。这引入了一个概念，即 ECs 不仅源自中胚层，而且还源自内胚层，在 Foxa2 谱系追踪小鼠胚胎中得到支持，因为鉴定出 FOXA2+细胞衍生的 CD31+ECs 整合了发育中胎儿肝脏的血管网络。
