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 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

doi:10.1038/s41467-022-31388-z

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 for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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.

Original language	English
Article number	3620
Journal	Nature Communications
Volume	13
Issue	1
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-022-31388-z
Publication status	Published - Dec 2022

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Wang, F., Ding, P., Liang, X., Ding, X., Brandt, C. B., Sjöstedt, E., Zhu, J., Bolund, S., Zhang, L., de Rooij, L. P. M. H., Luo, L., Wei, Y., Zhao, W., Lv, Z., Haskó, J., Li, R., Qin, Q., Jia, Y., Wu, W., ... Luo, Y. (2022). Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level. Nature Communications, 13(1), Article 3620. https://doi.org/10.1038/s41467-022-31388-z

@article{ee72aaaa0e92471f9d4afcb95edd3d03,

title = "Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level",

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.",

author = "Fei Wang and Peiwen Ding and Xue Liang and Xiangning Ding and Brandt, {Camilla Blunk} and Evelina Sj{\"o}stedt and Jiacheng Zhu and Saga Bolund and Lijing Zhang and {de Rooij}, {Laura P M H} and Lihua Luo and Yanan Wei and Wandong Zhao and Zhiyuan Lv and J{\'a}nos Hask{\'o} and Runchu Li and Qiuyu Qin and Yi Jia and Wendi Wu and Yuting Yuan and Mingyi Pu and Haoyu Wang and Aiping Wu and Lin Xie and Ping Liu and Fang Chen and Jacqueline Herold and Joanna Kalucka and Max Karlsson and Xiuqing Zhang and Helmig, {Rikke Bek} and Linn Fagerberg and Cecilia Lindskog and Fredrik Pont{\'e}n and Mathias Uhlen and Lars Bolund and Niels Jessen and Hui Jiang and Xun Xu and Huanming Yang and Peter Carmeliet and Jan Mulder and Dongsheng Chen and Lin Lin and Yonglun Luo",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-31388-z",

language = "English",

volume = "13",

journal = "Nature Communications",

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Wang, F, Ding, P, Liang, X, Ding, X , Brandt, CB, Sjöstedt, E, Zhu, J, Bolund, S, Zhang, L, de Rooij, LPMH, Luo, L, Wei, Y, Zhao, W, Lv, Z, Haskó, J, Li, R, Qin, Q, Jia, Y, Wu, W, Yuan, Y, Pu, M, Wang, H, Wu, A, Xie, L, Liu, P, Chen, F, Herold, J, Kalucka, J, Karlsson, M, Zhang, X, Helmig, RB, Fagerberg, L, Lindskog, C, Pontén, F, Uhlen, M, Bolund, L, Jessen, N, Jiang, H, Xu, X, Yang, H, Carmeliet, P, Mulder, J, Chen, D, Lin, L & Luo, Y 2022, 'Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level', Nature Communications, vol. 13, no. 1, 3620. https://doi.org/10.1038/s41467-022-31388-z

TY - JOUR

T1 - Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level

AU - Wang, Fei

AU - Ding, Peiwen

AU - Liang, Xue

AU - Ding, Xiangning

AU - Brandt, Camilla Blunk

AU - Sjöstedt, Evelina

AU - Zhu, Jiacheng

AU - Bolund, Saga

AU - Zhang, Lijing

AU - de Rooij, Laura P M H

AU - Luo, Lihua

AU - Wei, Yanan

AU - Zhao, Wandong

AU - Lv, Zhiyuan

AU - Haskó, János

AU - Li, Runchu

AU - Qin, Qiuyu

AU - Jia, Yi

AU - Wu, Wendi

AU - Yuan, Yuting

AU - Pu, Mingyi

AU - Wang, Haoyu

AU - Wu, Aiping

AU - Xie, Lin

AU - Liu, Ping

AU - Chen, Fang

AU - Herold, Jacqueline

AU - Kalucka, Joanna

AU - Karlsson, Max

AU - Zhang, Xiuqing

AU - Helmig, Rikke Bek

AU - Fagerberg, Linn

AU - Lindskog, Cecilia

AU - Pontén, Fredrik

AU - Uhlen, Mathias

AU - Bolund, Lars

AU - Jessen, Niels

AU - Jiang, Hui

AU - Xu, Xun

AU - Yang, Huanming

AU - Carmeliet, Peter

AU - Mulder, Jan

AU - Chen, Dongsheng

AU - Lin, Lin

AU - Luo, Yonglun

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85132918827&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-31388-z

DO - 10.1038/s41467-022-31388-z

M3 - Journal article

C2 - 35750885

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3620

ER -

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

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Author Correction: Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level (Nature Communications, (2022), 13, 1, (3620), 10.1038/s41467-022-31388-z)

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