原始造血、定向造血及血管生成过程中对Flk1的需求。

A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis.

作者信息

Shalaby F, Ho J, Stanford W L, Fischer K D, Schuh A C, Schwartz L, Bernstein A, Rossant J

机构信息

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

出版信息

Cell. 1997 Jun 13;89(6):981-90. doi: 10.1016/s0092-8674(00)80283-4.

DOI:10.1016/s0092-8674(00)80283-4

PMID:9200616

Abstract

Mouse embryos lacking the receptor tyrosine kinase, Flk1, die without mature endothelial and hematopoietic cells. To investigate the role of Flk1 during vasculogenesis and hematopoiesis, we examined the developmental potential of Flk1-/- embryonic stem cells in chimeras. We show that Flk1 is required cell autonomously for endothelial development. Furthermore, Flk1-/- cells do not contribute to primitive hematopoiesis in chimeric yolk sacs or definitive hematopoiesis in adult chimeras and chimeric fetal livers. We also demonstrate that cells lacking Flk1 are unable to reach the correct location to form blood islands, suggesting that Flk1 is involved in the movement of cells from the posterior primitive streak to the yolk sac and, possibly, to the intraembryonic sites of early hematopoiesis.

摘要

缺乏受体酪氨酸激酶Flk1的小鼠胚胎在没有成熟内皮细胞和造血细胞的情况下死亡。为了研究Flk1在血管生成和造血过程中的作用，我们检测了Flk1基因敲除胚胎干细胞在嵌合体中的发育潜能。我们发现Flk1对于内皮细胞发育是细胞自主所需的。此外，Flk1基因敲除细胞在嵌合卵黄囊中对原始造血没有贡献，在成年嵌合体和嵌合胎肝中对确定性造血也没有贡献。我们还证明，缺乏Flk1的细胞无法到达正确位置形成血岛，这表明Flk1参与了细胞从后原始条带向卵黄囊以及可能向胚胎早期造血的胚胎内位点的移动。