Single-Cell Transcriptomic Analysis of Salivary Gland Endothelial Cells.

A L Altrieth, J Kenney, D A Nelson, E G Suarez, V Gellatly, S Gabunia, M Larsen
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Abstract

Vascular endothelial cells have important tissue-specific functions in fibrosis and regeneration. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. To identify ligand-receptor interactions between endothelial cells and other cell types that may be important during fibrosis and regeneration, we used a reversible ductal ligation injury. To induce injury, a clip was applied to the primary ducts for 14 d, and to induce a regenerative response, the clip was subsequently removed for 5 d. To identify endothelial cell-produced factors, we used single-cell RNA sequencing of stromal-enriched cells from adult female submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells expressed many unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-d ligated, mock-ligated, and 5-d deligated stromal-enriched transcripts and lineage tracing revealed that endothelial cells retain their identity following ligation and recovery from injury. CellChat and NATMI were used to predict changes in ligand-receptor interactions from endothelial cells to other cells in response to ligation and deligation. CellChat and NATMI predicted that after ligation, interactions with fibroblasts, epithelial cells, and glial cells were increased, and following deligation, interactions with pericyte, glia, fibroblasts, and immune cells were increased. Some of the highest-ranked interactions predicted in ligated compared to mock endothelial cells were between glial cells via Col4a2-Cd93 and Jag2-Notch1, as well as epithelial cells via Pecam1-Cd38, while in deligated compared to ligated endothelial cells, the top interactions were between fibroblasts via Ntf3-Ntrk2, glial cells via Hspg2-Itgb1, and pericytes via Jam2-F11r. Understanding salivary gland endothelial cell signaling will inform future endothelial cell-based regenerative therapies.

唾液腺内皮细胞的单细胞转录组分析
血管内皮细胞在纤维化和再生过程中具有重要的组织特异性功能。在唾液腺中,内皮细胞是正常发育所必需的,但它们在成人唾液腺中的作用却大多不为人知。为了确定内皮细胞与其他细胞类型之间的配体-受体相互作用在纤维化和再生过程中的重要作用,我们使用了可逆性导管结扎损伤。为了诱导损伤,在原发性导管上放置夹子 14 天,为了诱导再生反应,随后移除夹子 5 天。为了确定内皮细胞产生的因子,我们对成年女性颌下腺和舌下腺的基质富集细胞进行了单细胞 RNA 测序。我们将唾液腺内皮细胞的转录谱与其他器官内皮细胞的转录谱进行了比较。唾液腺内皮细胞表达了许多独特的基因,并与结肠、小肠和肾脏的其他栅栏状内皮细胞在基因表达上有最大的重叠。对 14 天结扎、模拟结扎和 5 天脱落的基质富集转录本进行比较和系谱追踪发现,内皮细胞在结扎和损伤恢复后仍能保持其特性。CellChat 和 NATMI 被用来预测结扎和脱落后内皮细胞与其他细胞之间配体-受体相互作用的变化。根据 CellChat 和 NATMI 预测,在结扎后,与成纤维细胞、上皮细胞和神经胶质细胞的相互作用增加,而在去除结扎后,与包膜细胞、神经胶质细胞、成纤维细胞和免疫细胞的相互作用增加。与模拟内皮细胞相比,在已连接内皮细胞中预测的最高级相互作用是神经胶质细胞之间通过 Col4a2-Cd93 和 Jag2-Notch1 以及上皮细胞之间通过 Pecam1-Cd38 进行的相互作用,而与已连接内皮细胞相比,在已脱连接内皮细胞中预测的最高级相互作用是成纤维细胞之间通过 Ntf3-Ntrk2 进行的相互作用、神经胶质细胞之间通过 Hspg2-Itgb1 进行的相互作用以及周细胞之间通过 Jam2-F11r 进行的相互作用。了解涎腺内皮细胞信号转导将为未来基于内皮细胞的再生疗法提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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