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Single-cell transcriptome unveils unique transcriptomic signatures of human organ-specific endothelial cells

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Abstract

The heterogeneity of endothelial cells (ECs) across human tissues remains incompletely inventoried. We constructed an atlas of > 210,000 ECs derived from 38 regions across 24 human tissues. Our analysis reveals significant differences in transcriptome, phenotype, metabolism and transcriptional regulation among ECs from various tissues. Notably, arterial, venous, and lymphatic ECs shared more common markers in multiple tissues than capillary ECs, which exhibited higher heterogeneity. This diversity in capillary ECs suggests their greater potential as targets for drug development. ECs from different tissues and vascular beds were found to be associated with specific diseases. Importantly, tissue specificity of EC senescence is more determined by somatic site than by tissue type (e.g. subcutaneus adipose tissue and visceral adipose tissue). Additionally, sex-specific differences in brain EC senescence were observed. Our EC atlas offers valuble resoursce for identifying EC subclusters in single-cell datasets from body tissues or organoids, facilitating the screen of tissue-specific targeted therapies, and serving as a powerful tool for future discoveries.

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Data Availability

The processed expression matrices used and/or analysed during the current study have been deposited in the figshare (https://figshare.com/), under doi: 10. 6084 / m9. Figshare.25111283. In addition, we have created two ShinyCell app (https://niuruize0525.shinyapps.io/human_ecs_atlas/ and https://niuruize0525.shinyapps.io/human_tissues_ec_atlas/) that allows researchers to browse gene expression and to visualize the results. The code for this project is publicly available through GitHub (https://github.com/niuruize/Human_EC).

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Acknowledgements

We are grateful to Li Chen and Yi-Fei Sun for technical assistance. We are also grateful to Yi-Hang Li for initial help with data analysis. We are also grateful to xiyoucloud for providing computational infrastructure.

Funding

This study was supported by Doctoral Research Fund of the Second Affiliated Hospital of Kunming Medical University (Grant number 2023BS14), 535 Talent Project of First Affiliated Hospital of Kunming Medical University (Grant number 2024535Q09), Yunnan Fundamental Research Projects—Youth Project (Grant number 202401AU070009), Yunnan Provincial Department of Education Science Research Fund Project (Grant number 2023Y0644), and Doctoral research Fund of the First Affiliated Hospital of Kunming Medical University (Grant number 2022BS005).

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Author notes

  1. Rui-Ze Niu, Hong-Yan Xu and Hui Tian contributed equally to this study.

Authors and Affiliations

  1. Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, No.374 Dianmian Road, Wuhua District, Kunming, Yunnan, China

    Rui-Ze Niu, Hong-Yan Xu, Xiao-Lan Li & Juan He

  2. Mental Health Centre of Kunming Medical University, Kunming, Yunnan, China

    Rui-Ze Niu

  3. Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China

    Hui Tian

  4. Department of Dermatology and Venereology, The First Affiliated Hospital of Kunming Medical University, No.295 Xichang Road, Kunming, Yunnan, China

    Dan Zhang & Yu-Ye Li

  5. Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan, Hubei, China

    Chun-Yu He

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  1. Rui-Ze Niu
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Contributions

RZN, JH, and YYL conceptualized, acquired funding, and supervised this study. Data were processed, analyzed and visualized by HYX, HT, and CYH. The manuscript was drafted by NRZ, XLL and HYX, and was reviewed and edited by XLL, DZ, and JH. All authors discussed results and commented on the manuscript.

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Correspondence to Xiao-Lan Li, Yu-Ye Li or Juan He.

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Niu, RZ., Xu, HY., Tian, H. et al. Single-cell transcriptome unveils unique transcriptomic signatures of human organ-specific endothelial cells. Basic Res Cardiol 119, 973–999 (2024). https://doi.org/10.1007/s00395-024-01087-5

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