Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche.
Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche.
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DOI：
10.1016/j.devcel.2014.04.012
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发表时间：
2014-05-27
影响因子：
11.8
通讯作者：
North, Trista E.
中科院分区：
文献类型：
--
作者：
Carroll, Kelli J.;Esain, Virginie;Garnaas, Maija K.;Cortes, Mauricio;Dovey, Michael C.;Nissim, Sahar;Frechette, Gregory M.;Liu, Sarah Y.;Kwan, Wanda;Cutting, Claire C.;Harris, James M.;Gorelick, Daniel A.;Halpern, Marnie E.;Lawson, Nathan D.;Goessling, Wolfram;North, Trista E.
造血干细胞和祖细胞（HSPC）功能的遗传控制越来越多的了解，但很少有人知道的相互作用指定胚胎造血生态位。在这里，我们报告了17β-雌二醇（E2）通过拮抗VEGF信号传导和随后的生血内皮（HE）身份分配来影响AGM区域中runx 1 + HSPC的产生。在血管生态位发育（12- 24 hpf）期间暴露于外源性E2通过降低VEGFAa和下游动脉Notch途径组分的表达显著破坏flk 1+血管成熟、ephrinB 2+动脉身份和scl+ HE的特化; VEGFAa/Notch的热休克诱导挽救了E2介导的血液血管缺陷。相反，内源性E2活性的抑制增加了体细胞VEGF表达和血管靶向调节，转移了动脉/静脉命运和HE定位的分配;阻断E2信号传导允许静脉产生scl+/runx 1+细胞，独立于动脉身份获取。总之，这些数据表明，卵黄来源的雌激素设置的腹侧边界生血血管生态位规格拮抗VEGF调节的背腹侧限制。
The 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 17β-estradiol (E2) influences the 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 (12–24hpf) significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity and specification of scl+ HE by decreasing the expression of VEGFAa and downstream arterial Notch-pathway components; heat-shock induction of VEGFAa/Notch rescued E2-mediated hemato-vascular defects. Conversely, repression of endogenous E2-activity increased somitic VEGF expression and vascular-target regulation, shifting the 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 yolk-derived estrogen sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral limits of VEGF regulation.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
4.5
作者：
Bertrand S;Thisse B;Tavares R;Sachs L;Chaumot A;Bardet PL;Escrivà H;Duffraisse M;Marchand O;Safi R;Thisse C;Laudet V
通讯作者：
Laudet V
影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
2.7
作者：
Froehlicher, Mirjam;Liedtke, Anja;Eggen, Rik I. L.
通讯作者：
Eggen, Rik I. L.
DOI：
10.1073/pnas.0506886103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Covassin, LD;Villefranc, JA;Lawson, ND
通讯作者：
Lawson, ND