| First Author | Kataoka H | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 26 | Pages | 6975-86 |
| PubMed ID | 21911838 | Mgi Jnum | J:179111 |
| Mgi Id | MGI:5301076 | Doi | 10.1182/blood-2011-05-352658 |
| Citation | Kataoka H, et al. (2011) Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRalpha+ primitive mesoderm. Blood 118(26):6975-86 |
| abstractText | Etv2 (Ets Variant 2) has been shown to be an indispensable gene for the development of hematopoietic cells (HPCs)/endothelial cells (ECs). However, how Etv2 specifies the mesoderm-generating HPCs/ECs remains incompletely understood. In embryonic stem cell (ESC) differentiation culture and Etv2-null embryos, we show that Etv2 is dispensable for generating primitive Flk-1(+)/PDGFRalpha(+) mesoderm but is required for the progression of Flk-1(+)/PDGFRalpha(+) cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1(+)/PDGFRalpha(+) and failed to generate Flk-1(+)/PDGFRalpha(-) mesoderm. Flk-1(+)/Etv2(+) early embryonic cells showed significantly higher hemato-endothelial potential than the Flk-1(+)/Etv2(-) population, suggesting that Etv2 specifies a hemato-endothelial subset of Flk-1(+) mesoderm. Critical hemato-endothelial genes were severely down-regulated in Etv2-null Flk-1(+) cells. Among those genes Scl, Fli1, and GATA2 were expressed simultaneously with Etv2 in early embryos and seemed to be critical targets. Etv2 reexpression in Etv2-null cells restored the development of CD41(+), CD45(+), and VE-cadherin(+) cells. Expression of Scl or Fli1 alone could also restore HPCs/ECs in the Etv2-null background, indicating that these 2 genes are critical downstream targets. Furthermore, VEGF induced Etv2 potently and rapidly in Flk-1(+) mesoderm. We propose that Flk-1(+)/PDGFRalpha(+) primitive mesoderm is committed into Flk-1(+)/PDGFRalpha(-) vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment. |
