Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation.
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IF: 8.786
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Cited by: 4
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Datasets
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Abstract

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren's syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the first time, we analyzed and validated specific pathways defined by bulk RNAseq using Visium technology to determine activation of these pathways within the LG sections. This analysis suggests that altered metabolism and the hallmarks of inflammatory responses from both epithelial and immune cells drive inflammation. The most significant pathway enriched in upregulated DEGs was the "TYROBP Causal Network", that has not been described previously in SS. We also noted a significant decrease in lipid metabolism in the LG of the NOD.H-2b mice. Our data suggests that modulation of these pathways can provide a therapeutic strategy to treat ADDE.

Keywords

Seurat
Spatial Transcriptomics
RNA sequencing
TYROBP
chronic inflammation
lacrimal gland
lipid metabolism
macrophages
spatial transcriptomics
visium

MeSH terms

Mice
Animals
Lacrimal Apparatus
Mice, Inbred NOD
Transcriptome
Dry Eye Syndromes
Sjogren's Syndrome
Macrophages
Inflammation
Epithelium

Authors

Mauduit, Olivier
Delcroix, Vanessa
Umazume, Takeshi
de Paiva, Cintia S
Dartt, Darlene A
Makarenkova, Helen P