Spry1 is expressed in hemangioblasts and negatively regulates primitive hematopoiesis and endothelial cell function.
Spry1 is expressed in hemangioblasts and negatively regulates primitive hematopoiesis and endothelial cell function.
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DOI：
10.1371/journal.pone.0018374
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发表时间：
2011-04-01
期刊：
影响因子：
3.7
通讯作者：
Friesel R
中科院分区：
文献类型：
--
作者：
Yang X;Gong Y;Friesel R
Development of the hematopoietic and endothelial lineages derives from a common mesodermal precursor, the Flk1+ hemangioblast. However, the signaling pathways that regulate the development of hematopoietic and endothelial cells from this common progenitor cell remains incompletely understood. Using mouse models with a conditional Spry1 transgene, and a Spry1 knockout mouse, we investigated the role of Spry1 in the development of the endothelial and hematopoietic lineages during development. Quantitative RT-PCR analysis demonstrates that Spry1, Spry2, and Spry4 are expressed in Flk1+ hemangioblasts in vivo, and decline significantly in c-Kit+ and CD41+ hematopoietic progenitors, while expression is maintained in developing endothelial cells. Tie2-Cre-mediated over-expression of Spry1 results in embryonic lethality. At E9.5 Spry1;Tie2-Cre embryos show near normal endothelial cell development and vessel patterning but have reduced hematopoiesis. FACS analysis shows a reduction of primitive hematopoietic progenitors and erythroblastic cells in Spry1;Tie2-Cre embryos compared to controls. Colony forming assays confirm the hematopoietic defects in Spry1;Tie2-Cre transgenic embryos. Immunostaining shows a significant reduction of CD41 or CD71 and dpERK co-stained cells in Spry1;Tie2-Cre embryos compared to controls, whereas the number of VEC+ and dpERK co-stained cells is comparable. Compared to controls, Spry1;Tie2-Cre embryos also show a decrease in proliferation and an increase in apoptosis. Furthermore, loss of Spry1 results in an increase of CD41+ and CD71+ cells at E9.5 compared with controls. These data indicate that primitive hematopoietic cells derive from Tie2-expressing hemangioblasts and that Spry1 over expression inhibits primitive hematopoietic progenitor and erythroblastic cell development and expansion while having no obvious effect on endothelial cell development.
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影响因子：
4.3
作者：
Lee, Sangjin;Nguyen, Tri M. Bui;Kovalenko, Dmitry;Adhikari, Neeta;Grindle, Suzanne;Polster, Sean P.;Friesel, Robert;Ramakrishnan, Sundaram;Hall, Jennifer L.
通讯作者：
Hall, Jennifer L.
影响因子：
21.3
作者：
Hanafusa, Hiroshi;Matsumoto, Kunihiro;Nishida, Eisuke
通讯作者：
Nishida, Eisuke
影响因子：
2.7
作者：
Kisanuki, YY;Hammer, RE;Yanagisawa, M
通讯作者：
Yanagisawa, M
DOI：
10.1161/01.atv.0000163182.73190.f9
发表时间：
2005-05-01
影响因子：
8.7
作者：
Magnusson, PU;Ronca, R;Claesson-Welsh, L
通讯作者：
Claesson-Welsh, L
影响因子：
20.3
作者：
Okamoto, R;Ueno, M;Takakura, N
通讯作者：
Takakura, N