| http://purl.uniprot.org/citations/21483770 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21483770 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundDevelopment 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.Methodology/principal findingsQuantitative 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.Conclusions/significanceThese 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."xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0018374"xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/author | "Gong Y."xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/author | "Friesel R."xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/pages | "e18374"xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/title | "Spry1 is expressed in hemangioblasts and negatively regulates primitive hematopoiesis and endothelial cell function."xsd:string |
| http://purl.uniprot.org/citations/21483770 | http://purl.uniprot.org/core/volume | "6"xsd:string |
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