Submandibular gland tissue RNAseq and spatial transcriptome analyses in IgG4-related disease

Author:

Yamamoto Motohisa1ORCID,Kamekura Ryuta2ORCID,Uehara Masaaki1ORCID,Ichii Yuta13ORCID,Tanaka Tomonao1ORCID,Aochi Satsuki1ORCID,Takano Ken-ichi2ORCID

Affiliation:

1. Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan

2. Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medical , Sapporo, Japan

3. Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo , Toyko, Japan

Abstract

Abstract Objective To identify genes that could provide clues leading to the discovery of drugs to treat IgG4-related disease (IgG4-RD). Methods Submandibular gland tissue bulk RNAseq analysis of 45 cases with a definite diagnosis of IgG4-RD was integrated with Visium spatial transcriptome analysis of two cases to identify pathogenic genes expressed in tertiary lymphoid tissues. Results Bulk RNAseq and pathway analyses showed upregulation of cell cycle and T cell-related signals in IgG4-RD. Spatial transcriptome analysis identified the cluster corresponding to germinal centres and the top 38 common genes that showed significant variations in expression compared with other clusters. The top 20 genes were extracted by comparing the bulk RNAseq data. Network analysis identified CDK1 as the gene most strongly associated of the top 20 genes. Conclusion The CDK1 gene may be a regulator of the pathogenesis of IgG4-RD and provide clues for drug discovery.

Funder

JSPS KAKENHI

Ministry of Health, Labour and Welfare Research Program on Rare and Intractable Diseases

Takeda Science Foundation

Publisher

Oxford University Press (OUP)

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