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. Rooij, Lihua Luo, Yanan Wei, Wandong Zhao, Zhiyuan Lv, János Haskó, Runchu Li, Qiuyu Qin, Yi Jia, Wendi Wu, Yuting Yuan, Mingyi 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 () and Yonglun Luo ()
Additional contact information
Fei Wang: Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
Peiwen Ding: BGI-Shenzhen
Xue Liang: Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
Xiangning Ding: BGI-Shenzhen
Camilla Blunk Brandt: Aarhus University
Evelina Sjöstedt: Karolinska Institutet
Jiacheng Zhu: BGI-Shenzhen
Saga Bolund: Karolinska Institutet
Lijing Zhang: BGI-Shenzhen
Laura P. M. H. Rooij: Center for Cancer Biology, VIB
Lihua Luo: BGI-Shenzhen
Yanan Wei: BGI-Shenzhen
Wandong Zhao: BGI-Shenzhen
Zhiyuan Lv: BGI-Shenzhen
János Haskó: Aarhus University
Runchu Li: BGI-Shenzhen
Qiuyu Qin: BGI-Shenzhen
Yi Jia: BGI-Shenzhen
Wendi Wu: BGI-Shenzhen
Yuting Yuan: Binzhou Medical University
Mingyi Pu: BGI-Shenzhen
Haoyu Wang: BGI-Shenzhen
Aiping Wu: Peking Union Medical College
Lin Xie: MGI, BGI-Shenzhen
Ping Liu: MGI, BGI-Shenzhen
Fang Chen: MGI, BGI-Shenzhen
Jacqueline Herold: Aarhus University
Joanna Kalucka: Aarhus University
Max Karlsson: KTH-Royal Institute of Technology
Xiuqing Zhang: BGI-Shenzhen
Rikke Bek Helmig: Aarhus University Hospital
Linn Fagerberg: KTH-Royal Institute of Technology
Cecilia Lindskog: Genetics and Pathology, Uppsala University
Fredrik Pontén: Genetics and Pathology, Uppsala University
Mathias Uhlen: Karolinska Institutet
Lars Bolund: Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
Niels Jessen: Aarhus University Hospital
Hui Jiang: MGI, BGI-Shenzhen
Xun Xu: BGI-Shenzhen
Huanming Yang: BGI-Shenzhen
Peter Carmeliet: Aarhus University
Jan Mulder: Karolinska Institutet
Dongsheng Chen: BGI-Shenzhen
Lin Lin: Aarhus University
Yonglun Luo: Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31388-z

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