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

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  • Fei Wang
  • Peiwen Ding
  • 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 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
  • Yonglun Luo

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-beta, 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.

Original languageEnglish
Article number3620
JournalNature Communications
Volume13
Number of pages18
ISSN2041-1723
DOIs
Publication statusPublished - 2022

Bibliographical note

Correction: DOI 10.1038/s41467-022-34498-w

    Research areas

  • TO-MESENCHYMAL TRANSITION, GENE-EXPRESSION, MODEL, ATLAS, ANGIOGENESIS, DIFFERENTIATION, CONTRIBUTES, RESOLUTION, PROVIDE, HEALTH

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