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Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Sjögren’s Syndrome Salivary Glands

ABSTRACT: Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Sjögren’s Syndrome Salivary Glands

PROVIDER: PRJNA733146 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR14667228.fastq.gz	Fastqsanger.gz
	SRR14667229.fastq.gz	Fastqsanger.gz
	SRR14667230.fastq.gz	Fastqsanger.gz
	SRR14667231.fastq.gz	Fastqsanger.gz

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Project description:Primary Sjögren’s syndrome (SS or autoimmune epithelitis) is a relatively common autoimmune disorder that is primarily characterized by chronic lymphoepithelial inflammatory reactions in the exocrine glands, mainly the salivary and lachrymal glands. It may extend from disease confined to the exocrine glands (organ-specific exocrinopathy) to various extraglandular manifestations (systemic disease) and the development of B-cell lymphoma. Several studies from our laboratory had provided evidence for the strong implication of ductal salivary gland epithelial cells (SGEC) in the pathogenesis of Sjögren’s syndrome (SS), including the development of salivary gland infiltrating lesions and of adverse systemic clinical complications, such as the development of B-cell lymphoma. In fact, the comparative assessment of non-neoplastic SGEC lines derived from SS patients and disease controls had indicated that the ductal epithelia of SS patients manifest an “intrinsically activated” status that is associated with distinct aberrant phenotypic and functional features encountered in “inflamed” cells. Herein, using microarray analysis, we sought to comparatively analyze the constitutive gene expression in long-term cultured non-neoplastic SGEC lines derived from non-SS sicca control individuals and from SS patients. The study aimed to reveal the genes that are differentially expressed between SGEC lines derived from SS patients and controls, as well as between SGEC lines derived from SS patients with moderate lymphocytic infiltrations (focus score<2; SS-Group-1) and SS patients with severe lymphocytic infiltrations (focus score ≥2; SS-Group-2). The transcriptome profiling analysis presented herein lends further support to the intrinsic activation status of patients’ ductal epithelia and its association with distinct proinflammatory and metabolism-related gene signatures, which occur primarily among patients with heavy tissue infiltrates and high risk for lymphoma development.

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Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Sjögren’s Syndrome Salivary Glands

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