Heterogeneity in endothelial cells and widespread venous arterialization during early vascular development in mammals.

Heterogeneity in endothelial cells and widespread venous arterialization during early vascular development in mammals.
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哺乳动物早期血管发育过程中内皮细胞的异质性和广泛的静脉动脉化

DOI:
10.1038/s41422-022-00615-z
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发表时间:
2022-04
期刊:
影响因子:
44.1
通讯作者:
Lan Y
Lan Y
中科院分区:
生物学1区
文献类型:
--
作者:
Hou S;Li Z;Dong J;Gao Y;Chang Z;Ding X;Li S;Li Y;Zeng Y;Xin Q;Wang B;Ni Y;Ning X;Hu Y;Fan X;Hou Y;Li X;Wen L;Zhou B;Liu B;Tang F;Lan Y

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动脉生成而不是非特异性毛细血管扩张对于恢复患者受损组织的有效循环至关重要。对胚胎发育过程中动脉内皮细胞的起源和特化的解读将有助于对成人动脉形成的理解。然而,在早期胚胎血管生成过程中,内皮细胞多样化的过程和动静脉命运解决的分子事件在很大程度上仍然没有得到解决。在这里,我们构建了小鼠和人类胚胎中关键血管生成和血管生成事件发生的时间窗口期间血管内皮细胞(VEC)的单细胞转录组景观。我们发现了两种不同的动脉血管内皮细胞类型,主要动脉血管内皮细胞和动脉丛血管内皮细胞,以及胚胎内位于形态学上无法区分的血管丛中的血管内皮细胞之间出乎意料的分叉动静脉特征。使用新开发的Nr2f2CrexER小鼠模型和双重重组酶介导的交叉遗传方法,使用计算预测和静脉特征VEC的进一步谱系追踪,我们揭示了具有相当静脉特征的毛细血管的早期和广泛的动脉化。总之,我们的研究结果提供了前所未有的和全面的细节内皮异质性和谱系关系在早期血管生成阶段,并建立了一个新的模型关于早期胚胎内血管的动脉生成行为。
Arteriogenesis rather than unspecialized capillary expansion is critical for restoring effective circulation to compromised tissues in patients. Deciphering the origin and specification of arterial endothelial cells during embryonic development will shed light on the understanding of adult arteriogenesis. However, during early embryonic angiogenesis, the process of endothelial diversification and molecular events underlying arteriovenous fate settling remain largely unresolved in mammals. Here, we constructed the single-cell transcriptomic landscape of vascular endothelial cells (VECs) during the time window for the occurrence of key vasculogenic and angiogenic events in both mouse and human embryos. We uncovered two distinct arterial VEC types, the major artery VECs and arterial plexus VECs, and unexpectedly divergent arteriovenous characteristics among VECs that are located in morphologically undistinguishable vascular plexus intra-embryonically. Using computational prediction and further lineage tracing of venous-featured VECs with a newly developed Nr2f2CrexER mouse model and a dual recombinase-mediated intersectional genetic approach, we revealed early and widespread arterialization from the capillaries with considerable venous characteristics. Altogether, our findings provide unprecedented and comprehensive details of endothelial heterogeneity and lineage relationships at early angiogenesis stages, and establish a new model regarding the arteriogenesis behaviors of early intra-embryonic vasculatures.
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