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

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.

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. https://www.thno.org/v11p6461.htm
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Abstract

Graphic 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


Citation styles

APA
Li, Q., Zhu, Z., Wang, L., Lin, Y., Fang, H., Lei, J., Cao, T., Wang, G., Dang, E. (2021). Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin. Theranostics, 11(13), 6461-6476. https://doi.org/10.7150/thno.54917.

ACS
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.

NLM
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. https://www.thno.org/v11p6461.htm

CSE
Li Q, Zhu Z, Wang L, Lin Y, Fang H, Lei J, Cao T, Wang G, Dang E. 2021. Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin. Theranostics. 11(13):6461-6476.

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