Theranostics 2021; 11(13):6461-6476. doi:10.7150/thno.54917

Research Paper

Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin

Qingyang Li#, Zhenlai Zhu#, Lei Wang, Yiting Lin, Hui Fang, Jie Lei, Tianyu Cao, Gang Wang, Erle Dang

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P. R. China.
#These authors contributed equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li Q, Zhu Z, Wang L, Lin Y, Fang H, Lei J, Cao T, Wang G, Dang E. Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin. Theranostics 2021; 11(13):6461-6476. doi:10.7150/thno.54917. Available from https://www.thno.org/v11p6461.htm

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Abstract

Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery. Yet, their functional roles and heterogeneity in skin remain uncharacterized. We have used single-cell RNA sequencing (scRNA-seq) as a profiling strategy to investigate the tissue-specific features and intra-tissue heterogeneity in dermal ECs at single-cell level.

Methods: Skin tissues collected from 10 donors were subjected to scRNA-seq. Human dermal EC atlas of over 23,000 single-cell transcriptomes was obtained and further analyzed. Arteriovenous markers discovered in scRNA-seq were validated in human skin samples via immunofluorescence. To illustrate tissue-specific characteristics of dermal ECs, ECs from other human tissues were extracted from previously reported data and compared with our transcriptomic data.

Results: In comparison with ECs from other human tissues, dermal ECs possess unique characteristics in metabolism, cytokine signaling, chemotaxis, and cell adhesions. Within dermal ECs, 5 major subtypes were identified, which varied in molecular signatures and biological activities. Metabolic transcriptome analysis revealed a preference for oxidative phosphorylation in arteriole ECs when compared to capillary and venule ECs. Capillary ECs abundantly expressed HLA-II molecules, suggesting its immune-surveillance role. Post-capillary venule ECs, with high levels of adhesion molecules, were equipped with the capacity in immune cell arrest, adhesion, and infiltration.

Conclusion: Our study provides a comprehensive characterization of EC features and heterogeneity in human dermis and sets the stage for future research in identifying disease-specific alterations of dermal ECs in various dermatoses.

Keywords: vascular endothelial cells, single-cell RNA sequencing, skin vessel heterogeneity, skin arteriovenous markers, metabolic diversity