Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin.
Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin.
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单细胞转录组分析揭示人类皮肤中血管内皮细胞的异质性
作者：
Li Q;Zhu Z;Wang L;Lin Y;Fang H;Lei J;Cao T;Wang G;Dang E
血管内皮细胞（ECs）越来越被认为是细胞间串扰的积极参与者，而不是营养输送管道的被动衬里。然而，它们在皮肤中的功能作用和异质性仍未明确。我们使用单细胞RNA测序（scRNA-seq）作为分析策略，在单细胞水平上研究真皮内皮细胞的组织特异性特征和组织内异质性。方法：对10例供体皮肤组织进行scrna测序。获得了超过23,000个单细胞转录组的人类皮肤EC图谱并进一步分析。在scRNA-seq中发现的动静脉标记物通过免疫荧光在人体皮肤样品中验证。为了说明真皮内皮细胞的组织特异性特征，从先前报道的数据中提取了其他人体组织的内皮细胞，并与我们的转录组学数据进行了比较。结果：与来自人体其他组织的内皮细胞相比，真皮内皮细胞在代谢、细胞因子信号传导、趋化性和细胞粘附方面具有独特的特征。在真皮内皮细胞中，鉴定出5种主要亚型，它们在分子特征和生物学活性上各不相同。代谢转录组分析显示，与毛细血管和小静脉内皮细胞相比，小动脉内皮细胞更倾向于氧化磷酸化。毛细血管内皮细胞大量表达HLA-II分子，提示其免疫监视作用。毛细血管后小静脉内皮细胞具有高水平的粘附分子，具有免疫细胞阻滞、粘附和浸润的能力。结论：我们的研究提供了人类真皮EC特征和异质性的全面表征，并为未来研究确定各种皮肤病真皮EC的疾病特异性改变奠定了基础。
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.