Volume 32, No 4, Apr 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 4, April 2022: 333-348   |  Open Access

ORIGINAL ARTICLES

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

Siyuan Hou^1,2,† , Zongcheng Li^2,† , Ji Dong^4,† , Yun Gao^4,† , Zhilin Chang^5,† , Xiaochen Ding^5,† , Shuaili Li⁵ , Yunqiao Li⁵ , Yang Zeng² , Qian Xin⁵ , Baihan Wang⁵ , Yanli Ni² , Xiaowei Ning⁵ , Yuqiong Hu⁴ , Xiaoying Fan⁴ , Yu Hou⁴ , Xianlong Li² , Lu Wen^4,6 , Bin Zhou⁷ , Bing Liu^1,2,5,* , Fuchou Tang^4,6,8,* , Yu Lan^1,*

¹Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
²State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
³Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China
⁴Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, Beijing, China
⁵State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China
⁶Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China
⁷The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
⁸Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
^†These authors contributed equally: Siyuan Hou, Zongcheng Li, Ji Dong, Yun Gao, Zhilin Chang, Xiaochen Ding
Correspondence: Bing Liu(bingliu17@126.com)Fuchou Tang(tangfuchou@pku.edu.cn)Yu Lan(rainyblue_1999@126.com)

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.

https://doi.org/10.1038/s41422-022-00615-z

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