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

Author

Listed:
  • Fei Wang

    (Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
    Aarhus University
    BGI-Shenzhen)

  • Peiwen Ding

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • Xue Liang

    (Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
    University of Copenhagen)

  • Xiangning Ding

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • Camilla Blunk Brandt

    (Aarhus University
    Aarhus University Hospital)

  • Evelina Sjöstedt

    (Karolinska Institutet)

  • Jiacheng Zhu

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • Saga Bolund

    (Karolinska Institutet)

  • Lijing Zhang

    (BGI-Shenzhen
    University of Chinese Academy of Sciences
    MGI, BGI-Shenzhen)

  • Laura P. M. H. Rooij

    (Center for Cancer Biology, VIB
    Leuven Cancer Institute, KU Leuven)

  • Lihua Luo

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • Yanan Wei

    (BGI-Shenzhen
    Qingdao University)

  • Wandong Zhao

    (BGI-Shenzhen
    Qingdao University)

  • Zhiyuan Lv

    (BGI-Shenzhen
    Qingdao University)

  • János Haskó

    (Aarhus University)

  • Runchu Li

    (BGI-Shenzhen
    Qingdao University)

  • Qiuyu Qin

    (BGI-Shenzhen
    Qingdao University)

  • Yi Jia

    (BGI-Shenzhen
    Qingdao University)

  • Wendi Wu

    (BGI-Shenzhen
    Qingdao University)

  • Yuting Yuan

    (Binzhou Medical University)

  • Mingyi Pu

    (BGI-Shenzhen
    Qingdao University)

  • Haoyu Wang

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • Aiping Wu

    (Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Lin Xie

    (MGI, BGI-Shenzhen)

  • Ping Liu

    (MGI, BGI-Shenzhen)

  • Fang Chen

    (MGI, BGI-Shenzhen)

  • Jacqueline Herold

    (Aarhus University)

  • Joanna Kalucka

    (Aarhus University
    Aarhus University Hospital
    Aarhus University of Advanced Studies (AIAS), Aarhus University)

  • Max Karlsson

    (KTH-Royal Institute of Technology)

  • Xiuqing Zhang

    (BGI-Shenzhen
    University of Chinese Academy of Sciences)

  • 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
    KTH-Royal Institute of Technology)

  • Lars Bolund

    (Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
    Aarhus University)

  • Niels Jessen

    (Aarhus University Hospital)

  • Hui Jiang

    (MGI, BGI-Shenzhen)

  • Xun Xu

    (BGI-Shenzhen)

  • Huanming Yang

    (BGI-Shenzhen
    Chinese Academy of Sciences)

  • Peter Carmeliet

    (Aarhus University
    Center for Cancer Biology, VIB
    Leuven Cancer Institute, KU Leuven
    Khalifa University of Science and Technology)

  • Jan Mulder

    (Karolinska Institutet)

  • Dongsheng Chen

    (BGI-Shenzhen
    Peking Union Medical College
    Suzhou Institute of Systems Medicine)

  • Lin Lin

    (Aarhus University
    Aarhus University Hospital)

  • Yonglun Luo

    (Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
    Aarhus University
    BGI-Shenzhen
    Aarhus University Hospital)

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.

Suggested Citation

  • 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 , 2022. "Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31388-z
    DOI: 10.1038/s41467-022-31388-z
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    2. Yuyao Song & Zhichao Miao & Alvis Brazma & Irene Papatheodorou, 2023. "Benchmarking strategies for cross-species integration of single-cell RNA sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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