ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification

被引：265

作者：

Lee, Dongjun ^{[1
]}

Park, Changwon ^{[4
]}

Lee, Ho ^{[1
,2
]}

Lugus, Jesse J. ^{[3
,4
]}

Kim, Seok Hyung ^{[4
]}

Arentson, Elizabeth ^{[4
]}

Chung, Yun Shin ^{[4
]}

Gomez, Gustavo ^{[5
]}

Kyba, Michael ^{[6
]}

Lin, Shuo ^{[5
]}

Janknecht, Ralf ^{[7
]}

Lim, Dae-Sik ^{[1
]}

Choi, Kyunghee ^{[3
,4
]}

机构：

[1] Korea Adv Inst Sci & Technol, Natl Res Lab, Dept Biol Sci, Taejon 305701, South Korea

[2] Natl Canc Ctr, Goyangsi, Gyeonggi Do, South Korea

[3] Washington Univ, Sch Med, Mol Cell Biol Program, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[5] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[6] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75235 USA

[7] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA

来源：

CELL STEM CELL | 2008年 / 2卷 / 05期

关键词：

D O I：

10.1016/j.stem.2008.03.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

FLK1-expressing (FLK1(+)) mesoderm generates blood and vessels. Here, we show that combined BMP, Notch, and Wnt signaling is necessary for efficient FLK1(+) mesoderm formation from embryonic stem cells (ESCs). Inhibition of BMP, Notch, and Wnt signaling pathways greatly decreased the generation of FLK1(+) mesoderm and expression of the Ets transcription factor Er71. Enforced expression of ER71 in ESCs resulted in a robust induction of FLK1(+) mesoderm; rescued the generation of FLK1(+) mesoderm when blocked by BMP, Notch, and Wnt inhibition; and enhanced hematopoietic and endothelial cell generation. Er71-deficient mice had greatly reduced FLK1 expression, died early in gestation, and displayed severe blood and vessel defects that are highly reminiscent of the Flk1 null mouse phenotype. Collectively, we provide compelling evidence that ER71 functions downstream of BMP, Notch, and Wnt signals and regulates FLK1(+) mesoderm, blood, and vessel development.

引用

页码：497 / 507

页数：11

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