Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases
Issued Date
2024-01-01
Resource Type
ISSN
10614036
eISSN
15461718
Scopus ID
2-s2.0-85211588313
Pubmed ID
39627432
Journal Title
Nature Genetics
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Genetics (2024)
Suggested Citation
Tian C., Zhang Y., Tong Y., Kock K.H., Sim D.Y., Liu F., Dong J., Jing Z., Wang W., Gao J., Tan L.M., Han K.Y., Tomofuji Y., Nakano M., Buyamin E.V., Sonthalia R., Ando Y., Hatano H., Sonehara K., Moody J., Lin Q.X.X., Venkatesh P.N., Maitra A., Lim J., Kouno T., Kojima M., Suzuki A., Oh J.M., Myouzen K., Inoue G., Furukawa S., Abe M., Thungsatianpun N., Sarkar S., Nguantad S., Jevapatarakul D., Ghosh S., Chatterjee A., Chantaraamporn J., Sankaran S., Rayan N.A., Rajagopalan D., Yamamoto K., Suktitipat B., Pithukpakorn M., Chambers J.C., Carninci P., Matangkasombut P., Majumder P.P., Charoensawan V., Jin X., Loh M., Chambers J., Hon C.C., Choi M., Park J.E., Ishigaki K., Okamura T., Fujio K., Okada Y., Park W.Y., Shin J.W., Roca X., Prabhakar S., Liu B. Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases. Nature Genetics (2024). doi:10.1038/s41588-024-02019-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102433
Title
Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases
Author(s)
Tian C.
Zhang Y.
Tong Y.
Kock K.H.
Sim D.Y.
Liu F.
Dong J.
Jing Z.
Wang W.
Gao J.
Tan L.M.
Han K.Y.
Tomofuji Y.
Nakano M.
Buyamin E.V.
Sonthalia R.
Ando Y.
Hatano H.
Sonehara K.
Moody J.
Lin Q.X.X.
Venkatesh P.N.
Maitra A.
Lim J.
Kouno T.
Kojima M.
Suzuki A.
Oh J.M.
Myouzen K.
Inoue G.
Furukawa S.
Abe M.
Thungsatianpun N.
Sarkar S.
Nguantad S.
Jevapatarakul D.
Ghosh S.
Chatterjee A.
Chantaraamporn J.
Sankaran S.
Rayan N.A.
Rajagopalan D.
Yamamoto K.
Suktitipat B.
Pithukpakorn M.
Chambers J.C.
Carninci P.
Matangkasombut P.
Majumder P.P.
Charoensawan V.
Jin X.
Loh M.
Chambers J.
Hon C.C.
Choi M.
Park J.E.
Ishigaki K.
Okamura T.
Fujio K.
Okada Y.
Park W.Y.
Shin J.W.
Roca X.
Prabhakar S.
Liu B.
Zhang Y.
Tong Y.
Kock K.H.
Sim D.Y.
Liu F.
Dong J.
Jing Z.
Wang W.
Gao J.
Tan L.M.
Han K.Y.
Tomofuji Y.
Nakano M.
Buyamin E.V.
Sonthalia R.
Ando Y.
Hatano H.
Sonehara K.
Moody J.
Lin Q.X.X.
Venkatesh P.N.
Maitra A.
Lim J.
Kouno T.
Kojima M.
Suzuki A.
Oh J.M.
Myouzen K.
Inoue G.
Furukawa S.
Abe M.
Thungsatianpun N.
Sarkar S.
Nguantad S.
Jevapatarakul D.
Ghosh S.
Chatterjee A.
Chantaraamporn J.
Sankaran S.
Rayan N.A.
Rajagopalan D.
Yamamoto K.
Suktitipat B.
Pithukpakorn M.
Chambers J.C.
Carninci P.
Matangkasombut P.
Majumder P.P.
Charoensawan V.
Jin X.
Loh M.
Chambers J.
Hon C.C.
Choi M.
Park J.E.
Ishigaki K.
Okamura T.
Fujio K.
Okada Y.
Park W.Y.
Shin J.W.
Roca X.
Prabhakar S.
Liu B.
Author's Affiliation
RIKEN Center for Integrative Medical Sciences
Fondazione Human Technopole
Faculty of Science, Mahidol University
Siriraj Hospital
Graduate School of Medicine
Graduate School of Medicine
Lee Kong Chian School of Medicine
School of Biological Sciences
WPI Immunology Frontier Research Center, Osaka University
Korea Advanced Institute of Science and Technology
A-Star, Genome Institute of Singapore
Hiroshima University
NUS Yong Loo Lin School of Medicine
Suranaree University of Technology
Indian Statistical Institute, Kolkata
South China University of Technology
Osaka University
Samsung Medical Center, Sungkyunkwan university
National University of Singapore
Imperial College London
Mahidol University
Seoul National University College of Medicine
Shanxi Medical University
Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics
BGI Research
John C. Martin Centre for Liver Research and Innovations
Fondazione Human Technopole
Faculty of Science, Mahidol University
Siriraj Hospital
Graduate School of Medicine
Graduate School of Medicine
Lee Kong Chian School of Medicine
School of Biological Sciences
WPI Immunology Frontier Research Center, Osaka University
Korea Advanced Institute of Science and Technology
A-Star, Genome Institute of Singapore
Hiroshima University
NUS Yong Loo Lin School of Medicine
Suranaree University of Technology
Indian Statistical Institute, Kolkata
South China University of Technology
Osaka University
Samsung Medical Center, Sungkyunkwan university
National University of Singapore
Imperial College London
Mahidol University
Seoul National University College of Medicine
Shanxi Medical University
Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics
BGI Research
John C. Martin Centre for Liver Research and Innovations
Corresponding Author(s)
Other Contributor(s)
Abstract
Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in ~1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific. We identify 11,577 independent cis-splicing quantitative trait loci (sQTLs), 607 trans-sGenes and 107 dynamic sQTLs. Colocalization between cis-eQTLs and trans-sQTLs revealed a cell-type-specific regulatory relationship between HNRNPLL and PTPRC. We observed an enrichment of cis-sQTL effects in autoimmune and inflammatory disease heritability. Specifically, we functionally validated an Asian-specific sQTL disrupting the 5′ splice site of TCHP exon 4 that putatively modulates the risk of Graves’ disease in East Asian populations. Our work highlights the impact of ancestral diversity on splicing and provides a roadmap to dissect its role in complex diseases at single-cell resolution.