Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm
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...
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| Veröffentlicht in: | Blood 2011-12, Vol.118 (26), p.6975-6986 |
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| creator | Kataoka, Hiroshi Hayashi, Misato Nakagawa, Reiko Tanaka, Yosuke Izumi, Naoki Nishikawa, Satomi Jakt, Martin Lars Tarui, Hiroshi Nishikawa, Shin-Ichi |
| description | 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+/PDGFRα+ mesoderm but is required for the progression of Flk-1+/PDGFRα+ cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1+/PDGFRα+ and failed to generate Flk-1+/PDGFRα− 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+/PDGFRα+ primitive mesoderm is committed into Flk-1+/PDGFRα− vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment. |
| doi_str_mv | 10.1182/blood-2011-05-352658 |
| format | Article |
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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+/PDGFRα+ mesoderm but is required for the progression of Flk-1+/PDGFRα+ cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1+/PDGFRα+ and failed to generate Flk-1+/PDGFRα− 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+/PDGFRα+ primitive mesoderm is committed into Flk-1+/PDGFRα− vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2011-05-352658</identifier><identifier>PMID: 21911838</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Cadherins - genetics ; Cadherins - metabolism ; Cell Differentiation - genetics ; Cell Line ; Cells, Cultured ; Embryo, Mammalian - cytology ; Embryo, Mammalian - embryology ; Embryo, Mammalian - metabolism ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Endothelium, Vascular - cytology ; Endothelium, Vascular - embryology ; Endothelium, Vascular - metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Hematopoietic System - cytology ; Hematopoietic System - embryology ; Hematopoietic System - metabolism ; In Situ Hybridization ; Leukocyte Common Antigens - genetics ; Leukocyte Common Antigens - metabolism ; Mesoderm - embryology ; Mesoderm - metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Microscopy, Fluorescence ; Oligonucleotide Array Sequence Analysis ; Platelet Membrane Glycoprotein IIb - genetics ; Platelet Membrane Glycoprotein IIb - metabolism ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><ispartof>Blood, 2011-12, Vol.118 (26), p.6975-6986</ispartof><rights>2011 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c291t-5e6263e9b0b4069b855bf1fbde60ce0035889ae066e0fd9612ec25e367906a83</citedby><cites>FETCH-LOGICAL-c291t-5e6263e9b0b4069b855bf1fbde60ce0035889ae066e0fd9612ec25e367906a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21911838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kataoka, Hiroshi</creatorcontrib><creatorcontrib>Hayashi, Misato</creatorcontrib><creatorcontrib>Nakagawa, Reiko</creatorcontrib><creatorcontrib>Tanaka, Yosuke</creatorcontrib><creatorcontrib>Izumi, Naoki</creatorcontrib><creatorcontrib>Nishikawa, Satomi</creatorcontrib><creatorcontrib>Jakt, Martin Lars</creatorcontrib><creatorcontrib>Tarui, Hiroshi</creatorcontrib><creatorcontrib>Nishikawa, Shin-Ichi</creatorcontrib><title>Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm</title><title>Blood</title><addtitle>Blood</addtitle><description>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+/PDGFRα+ mesoderm but is required for the progression of Flk-1+/PDGFRα+ cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1+/PDGFRα+ and failed to generate Flk-1+/PDGFRα− 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+/PDGFRα+ primitive mesoderm is committed into Flk-1+/PDGFRα− vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment.</description><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - embryology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - embryology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Hematopoietic System - cytology</subject><subject>Hematopoietic System - embryology</subject><subject>Hematopoietic System - metabolism</subject><subject>In Situ Hybridization</subject><subject>Leukocyte Common Antigens - genetics</subject><subject>Leukocyte Common Antigens - metabolism</subject><subject>Mesoderm - embryology</subject><subject>Mesoderm - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Fluorescence</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Platelet Membrane Glycoprotein IIb - genetics</subject><subject>Platelet Membrane Glycoprotein IIb - metabolism</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Time Factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFOwzAQRS0EoqVwA4SyY1GFjp3YjTdIqLSlUiVQ1b2V2BPJkDTFTiJxLC7CmUhJYclqNm_-n3mEXFO4ozRhk6yoKhMyoDQEHkacCZ6ckCHlLAkBGJySIQCIMJZTOiAX3r8C0Dhi_JwMGJVdRpQMyWpet2wy30xpYHem0eiDNvW6KVIXlOgrg64McleVwaJ4o-OXx-Vi8_U5DvbOlra2Lf5Rl-QsTwuPV8c5ItvFfDt7CtfPy9XsYR1qJmkdchRMRCgzyGIQMks4z3KaZwYFaASIeJLIFEEIhNxIQRlqxjESUwkiTaIRue1j9656b9DXqrReY1GkO6waryRlIo4jzjsy7kntKu8d5upwdOo-FAV1UKh-FKqDQgVc9Qq7tZtjQZOVaP6Wfp11wH0PYPdla9Epry3uNBrrUNfKVPb_hm-HkIFr</recordid><startdate>20111222</startdate><enddate>20111222</enddate><creator>Kataoka, Hiroshi</creator><creator>Hayashi, Misato</creator><creator>Nakagawa, Reiko</creator><creator>Tanaka, Yosuke</creator><creator>Izumi, Naoki</creator><creator>Nishikawa, Satomi</creator><creator>Jakt, Martin Lars</creator><creator>Tarui, Hiroshi</creator><creator>Nishikawa, Shin-Ichi</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20111222</creationdate><title>Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm</title><author>Kataoka, Hiroshi ; Hayashi, Misato ; Nakagawa, Reiko ; Tanaka, Yosuke ; Izumi, Naoki ; Nishikawa, Satomi ; Jakt, Martin Lars ; Tarui, Hiroshi ; Nishikawa, Shin-Ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c291t-5e6263e9b0b4069b855bf1fbde60ce0035889ae066e0fd9612ec25e367906a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - metabolism</topic><topic>Cadherins - genetics</topic><topic>Cadherins - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - embryology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - embryology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Hematopoietic System - cytology</topic><topic>Hematopoietic System - embryology</topic><topic>Hematopoietic System - metabolism</topic><topic>In Situ Hybridization</topic><topic>Leukocyte Common Antigens - genetics</topic><topic>Leukocyte Common Antigens - metabolism</topic><topic>Mesoderm - embryology</topic><topic>Mesoderm - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Fluorescence</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Platelet Membrane Glycoprotein IIb - genetics</topic><topic>Platelet Membrane Glycoprotein IIb - metabolism</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Time Factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kataoka, Hiroshi</creatorcontrib><creatorcontrib>Hayashi, Misato</creatorcontrib><creatorcontrib>Nakagawa, Reiko</creatorcontrib><creatorcontrib>Tanaka, Yosuke</creatorcontrib><creatorcontrib>Izumi, Naoki</creatorcontrib><creatorcontrib>Nishikawa, Satomi</creatorcontrib><creatorcontrib>Jakt, Martin Lars</creatorcontrib><creatorcontrib>Tarui, Hiroshi</creatorcontrib><creatorcontrib>Nishikawa, Shin-Ichi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kataoka, Hiroshi</au><au>Hayashi, Misato</au><au>Nakagawa, Reiko</au><au>Tanaka, Yosuke</au><au>Izumi, Naoki</au><au>Nishikawa, Satomi</au><au>Jakt, Martin Lars</au><au>Tarui, Hiroshi</au><au>Nishikawa, Shin-Ichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2011-12-22</date><risdate>2011</risdate><volume>118</volume><issue>26</issue><spage>6975</spage><epage>6986</epage><pages>6975-6986</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>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+/PDGFRα+ mesoderm but is required for the progression of Flk-1+/PDGFRα+ cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1+/PDGFRα+ and failed to generate Flk-1+/PDGFRα− 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+/PDGFRα+ primitive mesoderm is committed into Flk-1+/PDGFRα− vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21911838</pmid><doi>10.1182/blood-2011-05-352658</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, CD - genetics Antigens, CD - metabolism Cadherins - genetics Cadherins - metabolism Cell Differentiation - genetics Cell Line Cells, Cultured Embryo, Mammalian - cytology Embryo, Mammalian - embryology Embryo, Mammalian - metabolism Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Endothelium, Vascular - cytology Endothelium, Vascular - embryology Endothelium, Vascular - metabolism Gene Expression Profiling Gene Expression Regulation, Developmental Hematopoietic System - cytology Hematopoietic System - embryology Hematopoietic System - metabolism In Situ Hybridization Leukocyte Common Antigens - genetics Leukocyte Common Antigens - metabolism Mesoderm - embryology Mesoderm - metabolism Mice Mice, Knockout Mice, Transgenic Microscopy, Fluorescence Oligonucleotide Array Sequence Analysis Platelet Membrane Glycoprotein IIb - genetics Platelet Membrane Glycoprotein IIb - metabolism Receptor, Platelet-Derived Growth Factor alpha - genetics Receptor, Platelet-Derived Growth Factor alpha - metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors Transcription Factors - genetics Transcription Factors - metabolism Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm |
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