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Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche

dc.contributor.authorCarroll, Kelli J.
dc.contributor.authorEsain, Virginie
dc.contributor.authorGarnaas, Maija K.
dc.contributor.authorCortes, Mauricio
dc.contributor.authorDovey, Michael C.
dc.contributor.authorNissim, Sahar
dc.contributor.authorFrechette, Gregory M.
dc.contributor.authorLiu, Sarah Y.
dc.contributor.authorKwan, Wanda
dc.contributor.authorCutting, Claire C.
dc.contributor.authorHarris, James M.
dc.contributor.authorGorelick, Daniel A.
dc.contributor.authorHalpern, Marnie E.
dc.contributor.authorLawson, Nathan D.
dc.contributor.authorGoessling, Wolfram
dc.contributor.authorNorth, Trista E.
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:01:32Z
dc.date.available2022-08-23T17:01:32Z
dc.date.issued2014-05-27
dc.date.submitted2014-06-10
dc.identifier.citationCarroll KJ, Esain V, Garnaas MK, Cortes M, Dovey MC, Nissim S, Frechette GM, Liu SY, Kwan W, Cutting CC, Harris JM, Gorelick DA, Halpern ME, Lawson ND, Goessling W, North TE. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell. 2014 May 27;29(4):437-53. doi: 10.1016/j.devcel.2014.04.012. <a href="http://dx.doi.org/10.1016/j.devcel.2014.04.012">Link to article on publisher's site</a>
dc.identifier.issn1534-5807 (Linking)
dc.identifier.doi10.1016/j.devcel.2014.04.012
dc.identifier.pmid24871948
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44031
dc.description.abstractGenetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17beta-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects. Conversely, repression of endogenous E2 activity increased somitic VEGF expression and vascular target regulation, shifting assignment of arterial/venous fate and HE localization; blocking E2 signaling allowed venous production of scl+/runx1+ cells, independent of arterial identity acquisition. Together, these data suggest that yolk-derived E2 sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral regulatory limits of VEGF.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24871948&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.devcel.2014.04.012
dc.subjectCell and Developmental Biology
dc.subjectCellular and Molecular Physiology
dc.subjectGenetics and Genomics
dc.titleEstrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche
dc.typeJournal Article
dc.source.journaltitleDevelopmental cell
dc.source.volume29
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/246
dc.identifier.contextkey5673508
html.description.abstract<p>Genetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17beta-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects. Conversely, repression of endogenous E2 activity increased somitic VEGF expression and vascular target regulation, shifting assignment of arterial/venous fate and HE localization; blocking E2 signaling allowed venous production of scl+/runx1+ cells, independent of arterial identity acquisition. Together, these data suggest that yolk-derived E2 sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral regulatory limits of VEGF.</p>
dc.identifier.submissionpathpgfe_pp/246
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages437-53


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