Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level

Fei Wang, Peiwen Ding, Xue Liang, Xiangning Ding, Camilla Blunk Brandt, Evelina Sjöstedt, Jiacheng Zhu, Saga Bolund, Lijing Zhang, Laura P M H de Rooij, Lihua Luo, Yanan Wei, Wandong Zhao, Zhiyuan Lv, János Haskó, Runchu Li, Qiuyu Qin, Yi Jia, Wendi Wu, Yuting YuanMingyi Pu, Haoyu Wang, Aiping Wu, Lin Xie, Ping Liu, Fang Chen, Jacqueline Herold, Joanna Kalucka, Max Karlsson, Xiuqing Zhang, Rikke Bek Helmig, Linn Fagerberg, Cecilia Lindskog, Fredrik Pontén, Mathias Uhlen, Lars Bolund, Niels Jessen, Hui Jiang, Xun Xu, Huanming Yang, Peter Carmeliet, Jan Mulder, Dongsheng Chen*, Lin Lin*, Yonglun Luo*

*Corresponding author af dette arbejde

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Abstract

Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-β, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.

OriginalsprogEngelsk
Artikelnummer3620
TidsskriftNature Communications
Vol/bind13
Nummer1
ISSN2041-1723
DOI
StatusUdgivet - jun. 2022

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