Erythropoiesis and vasculogenesis in embryoid bodies lacking visceral yolk sac endoderm
Erythropoiesis and vasculogenesis in embryoid bodies lacking visceral yolk sac endoderm
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DOI：
10.1182/blood.v88.10.3720.bloodjournal88103720
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发表时间：
1996-11-15
期刊：
影响因子：
20.3
通讯作者：
Wilson, DB
中科院分区：
文献类型：
--
作者：
Bielinska, M;Narita, N;Wilson, DB
在小鼠胚胎发育过程中，首先在卵黄囊内脏内胚层和中胚层之间的血岛上形成造血细胞和内皮细胞。内脏内胚层在原始造血和血管生成中的作用尚不清楚。我们使用缺乏GATA-4的小鼠胚胎干细胞(ES细胞)来评估内脏内胚层缺乏对血细胞和血管形成的影响。GATA-4是一种在卵黄囊内胚层表达的转录因子。当在体外分化时，这些突变的类胚体不会形成外部内脏内胚层。我们发现，无论是在悬浮培养中生长还是附着在底物上的GATA4-/-类胚体，在原始造血和血管生成方面都存在缺陷，表现为缺乏可识别的血岛和血管通道，以及原始红细胞标志物epsilon(V)-珠蛋白的表达减少。突变的拟胚体中内皮细胞转录因子Flk-1、Flt-1和血小板-内皮细胞黏附分子(PECAM)的表达不受影响，Gata4-/-ES细胞在甲基纤维素或Matrigel中培养时仍具有向原始红细胞和内皮细胞分化的能力。通过将Gata4-/-ES细胞注射到8-细胞期的rosa26转基因动物胚胎中而产生的嵌合小鼠的分析表明，Gata4-/-ES细胞在体内与内脏内胚层并列时可以形成血岛和血管。内脏内胚层对原始红细胞或内皮细胞的分化不是必需的，但该细胞层在卵黄囊血岛和血管的形成和组织中起重要作用。(C)1996年，由美国线虫学会提供。
During mouse embryogenesis the first hematopoietic and endothelial cells form in blood islands located between layers of visceral endoderm and mesoderm in the yolk sac. The role of visceral endoderm in primitive hematopoiesis and vasculogenesis is not well understood. We have assessed the consequences of a lack of visceral endoderm on blood cell and vessel formation using embryoid bodies derived from mouse embryonic stem (ES) cells deficient in GATA-4, a transcription factor expressed in yolk sac endoderm. When differentiated in vitro, these mutant embryoid bodies do not develop an external visceral endoderm layer. We found that Gata4-/- embryoid bodies, grown either in suspension culture or attached to a substratum, are defective in primitive hematopoiesis and vasculogenesis as evidenced by a lack of recognizable blood islands and vascular channels and a reduction in the expression of the primitive erythrocyte marker epsilon(v)-globin. Expression of the endothelial cell transcripts Flk-1, Flt-1, and platelet-endothelial cell adhesion molecule (PECAM) was not affected in the mutant embryoid bodies, Gata4-/- ES cells retained the capacity to differentiate into primitive erythroblasts and endothelial cells when cultured in methylcellulose or matrigel. Analysis of chimeric mice, generated by injecting Gata4-/- ES cells into 8-cell stage embryos of ROSA26 transgenic animals, showed that Gata4-/- ES cells can form blood islands and vessels when juxtaposed to visceral endoderm in vivo. We conclude that the visceral endoderm is not essential for the differentiation of primitive erythrocytes or endothelial cells, but this cell layer plays an important role in the formation and organization of yolk sac blood islands and vessels. (C) 1996 by The American Society of Nematology.