a Primitive ECs (at ~E8–E8.5) must choose either a arterial or venous fate. Arterial ECs are distinguished by the arterial marker Gja5; venous ECs are distinguished by the venous marker Nr2f2. Primitive arterial ECs continue on to early arterial ECs (between E8.5 and E9.5) that are distinguished by the arterial markers Sox17, Gja5, and surface marker CD44. b Between E9.5 and E10.5 early arterial ECs either adopt a hematopoietic fate and become HECs or maintain their arterial EC fate and become late arterial ECs characterized by arterial markers such as Ltbp4. HECs are characterized by the expression of arterial markers and hematopoietic markers such as Runx1, Gfi1, Myb, and Spi1. The fate of HEC is a pre-HSC (~E10.5–E11.0), which gains cell surface marker CD41 and stronger expression of hematopoietic genes Runx1, Myb, Spn, and Spi1. HECs and pre-HSCs are both marked by the novel HEC signature gene Neurl3, which can be used to isolate these cells using a Neurl3:EGFP reporter mouse. Both HECs and pre-HSCs are functionally characterized by the ability to form both ECs and hematopoietic cells in culture. However, HECs maintain stronger endothelial potential relative to pre-HSCs.
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