Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice.

Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice.
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DOI:
10.1016/j.csbj.2022.11.054
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发表时间:
2023
影响因子:
6
通讯作者:
Peng, Jinrong
Peng, Jinrong
中科院分区:
生物学2区
文献类型:
--
作者:
Huang, Heping;Gao, Ce;Wang, Shuai;Wu, Fen;Wei, Jinsong;Peng, Jinrong

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肥胖影响多个器官/组织的功能,包括外分泌器官唾液腺。然而,肥胖对唾液腺中转录组和细胞组成的影响尚未通过批量RNA测序和单细胞RNA测序进行研究。此外,三大唾液腺之一的舌下腺的细胞类型还没有通过单细胞RNA测序的方法来表征。本研究发现,肥胖小鼠三大唾液腺的组织结构未受到明显影响。大量RNA测序分析表明,在肥胖小鼠的三个主要唾液腺中观察到的最突出的变化是与免疫应答相关的转录组的动员和与唾液腺分泌功能相关的基因的下调。基于单细胞RNA测序分析,我们首次鉴定并注释了舌下腺中的17个细胞簇,发现肥胖改变了肥胖小鼠主要腺体中免疫细胞和分泌细胞的相对组成。整体RNA测序和单细胞RNA测序数据的综合分析证实了肥胖小鼠三大唾液腺中免疫应答基因的激活和分泌功能的妥协。因此,在肥胖小鼠的三个主要唾液腺中,细胞外基质蛋白的分泌显著减少。这些结果为了解肥胖对唾液腺的影响提供了新的分子见解。
Obesity affects the function of multiple organs/tissues including the exocrine organ salivary glands. However, the effects of obesity on transcriptomes and cell compositions in the salivary glands have yet been studied by bulk RNA-sequencing and single-cell RNA-sequencing. Besides, the cell types in the sublingual gland, one of the three major salivary glands, have yet been characterized by the approach of single-cell RNA-sequencing. In this report, we find that the histological structure of the three major salivary glands are not obviously affected in the obese mice. Bulk RNA-sequencing analysis shows that the most prominent changes observed in the three major salivary glands of the obese mice are the mobilization of transcriptomes related to the immune response and down-regulation of genes related to the secretory function of the salivary glands. Based on single-cell RNA-sequencing analysis, we identify and annotate 17 cell clusters in the sublingual gland for the first time, and find that obesity alters the relative compositions of immune cells and secretory cells in the major glands of obese mice. Integrative analysis of the bulk RNA-sequencing and single-cell RNA-sequencing data confirms the activation of immune response genes and compromise of secretory function in the three major salivary glands of obese mice. Consequently, the secretion of extracellular matrix proteins is significantly reduced in the three major salivary glands of obese mice. These results provide new molecular insights into understanding the effect of obesity on salivary glands.
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