{"id":4608,"date":"2025-12-17T14:34:10","date_gmt":"2025-12-17T07:34:10","guid":{"rendered":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/?p=4608"},"modified":"2025-12-17T14:34:55","modified_gmt":"2025-12-17T07:34:55","slug":"single-cell-rna-sequencing-of-peripheral-blood-links-cell-type-specific-regulation-of-splicing-to-autoimmune-and-inflammatory-diseases","status":"publish","type":"post","link":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/single-cell-rna-sequencing-of-peripheral-blood-links-cell-type-specific-regulation-of-splicing-to-autoimmune-and-inflammatory-diseases\/","title":{"rendered":"Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases"},"content":{"rendered":"<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div class=\"title\"><\/div>\n<p class=\"chapter-para\">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&#8242; splice site of TCHP exon 4 that putatively modulates the risk of Graves&#8217; 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.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39627432\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/39627432\/<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>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, [&#8230;]\n","protected":false},"author":6,"featured_media":4610,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-4608","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-innovation-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/single-cell-rna-sequencing-of-peripheral-blood-links-cell-type-specific-regulation-of-splicing-to-autoimmune-and-inflammatory-diseases\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"og:description\" content=\"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, [...]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/single-cell-rna-sequencing-of-peripheral-blood-links-cell-type-specific-regulation-of-splicing-to-autoimmune-and-inflammatory-diseases\/\" \/>\n<meta property=\"og:site_name\" content=\"\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/SIBBprogram\/\" \/>\n<meta property=\"article:published_time\" content=\"2025-12-17T07:34:10+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-12-17T07:34:55+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/wp-content\/uploads\/2025\/12\/41588_2024_2019_Fig1_HTML.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"722\" \/>\n\t<meta property=\"og:image:height\" content=\"510\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Poorintra Sakuna\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Poorintra Sakuna\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" 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