{"id":12497,"date":"2023-07-12T11:45:54","date_gmt":"2023-07-12T09:45:54","guid":{"rendered":"https:\/\/new.sano.science\/?post_type=research&#038;p=12497"},"modified":"2024-01-05T14:08:01","modified_gmt":"2024-01-05T13:08:01","slug":"an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-%ce%b1-synuclein","status":"publish","type":"research","link":"https:\/\/sano.science\/research\/an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-%ce%b1-synuclein\/","title":{"rendered":"An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of \u03b1-synuclein\u00a0"},"content":{"rendered":"\n<h2 class=\"wp-block-heading eplus-wrapper\">Kara, Eleanna; Crimi, Alessandro; Wiedmer, Anne; Hardy, John; Hyman, Bradley T.; Aguzzi, Adriano<\/h2>\n\n\n\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n<p class=\" eplus-wrapper\">Neuropathological and experimental evidence suggests that the cell-to-cell transfer of \u03b1-synuclein has an important role in the pathogenesis of Parkinson\u2019s disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of \u03b1-synuclein. A genetically encoded reporter, GFP-2A-\u03b1Synuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing \u03b1-synuclein. We find that 38 genes regulate the transfer of \u03b1-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of \u03b1-synuclein spread.<\/p>\n\n\n\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n\n\n\n\t\n    \n        \n\t\t\t<a href=\"https:\/\/dx.doi.org\/https:\/\/doi.org\/10.1016\/j.celrep.2021.109189\" target=\"_blank\" rel= \"noopener noreferrer nofollow\" class=\"button primary \">\n\n\t\t\t\t<span>\n\t\t\t\t\tREAD HERE\n\t\t\t\t<\/span>\n\n\t\t\t<\/a>\n\n        \n    \n","protected":false},"excerpt":{"rendered":"<p>In: 2021.<\/p>\n","protected":false},"featured_media":0,"template":"","research_type":[8],"research_team":[15],"class_list":["post-12497","research","type-research","status-publish","hentry","research_type-publications","research_team-computational-neuroscience"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.3 (Yoast SEO v27.3) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of \u03b1-synuclein\u00a0 - Centre for Computational Personalized Medicine<\/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:\/\/sano.science\/research\/an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-\u03b1-synuclein\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of \u03b1-synuclein\u00a0\" \/>\n<meta property=\"og:description\" content=\"In: 2021.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/sano.science\/research\/an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-\u03b1-synuclein\/\" \/>\n<meta property=\"og:site_name\" content=\"Centre for Computational Personalized Medicine\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/sano.science\/\" \/>\n<meta property=\"article:modified_time\" content=\"2024-01-05T13:08:01+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:site\" content=\"@sanoscience\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/sano.science\\\/research\\\/an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-%ce%b1-synuclein\\\/\",\"url\":\"https:\\\/\\\/sano.science\\\/research\\\/an-integrated-genomic-approach-to-dissect-the-genetic-landscape-regulating-the-cell-to-cell-transfer-of-%ce%b1-synuclein\\\/\",\"name\":\"An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of \u03b1-synuclein\u00a0 - 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However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of \u03b1-synuclein. A genetically encoded reporter, GFP-2A-\u03b1Synuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing \u03b1-synuclein. We find that 38 genes regulate the transfer of \u03b1-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of \u03b1-synuclein spread.<\/p>\n","innerContent":["\n<p class=\" eplus-wrapper\">Neuropathological and experimental evidence suggests that the cell-to-cell transfer of \u03b1-synuclein has an important role in the pathogenesis of Parkinson\u2019s disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of \u03b1-synuclein. A genetically encoded reporter, GFP-2A-\u03b1Synuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing \u03b1-synuclein. We find that 38 genes regulate the transfer of \u03b1-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of \u03b1-synuclein spread.<\/p>\n"]},{"blockName":"core\/spacer","attrs":{"height":"50px","epAnimationGeneratedClass":"edplus_anim-me7JZO","epGeneratedClass":"eplus-wrapper"},"innerBlocks":[],"innerHTML":"\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n","innerContent":["\n<div style=\"height:50px\" aria-hidden=\"true\" class=\"wp-block-spacer eplus-wrapper\"><\/div>\n"]},{"blockName":"acf\/button","attrs":{"title":"READ HERE","button_type":"link","url":"https:\/\/dx.doi.org\/https:\/\/doi.org\/10.1016\/j.celrep.2021.109189","button_style":"primary","target":"_blank","button_extra_classes":""},"innerBlocks":[],"innerHTML":"","innerContent":[]}],"meta_data":{"is_automatically_other_posts":true,"number_of_posts":"3","is_automatically_check_also_posts":true},"_links":{"self":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/12497","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research"}],"about":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/types\/research"}],"version-history":[{"count":5,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/12497\/revisions"}],"predecessor-version":[{"id":14760,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research\/12497\/revisions\/14760"}],"wp:attachment":[{"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/media?parent=12497"}],"wp:term":[{"taxonomy":"research_type","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_type?post=12497"},{"taxonomy":"research_team","embeddable":true,"href":"https:\/\/sano.science\/index.php\/wp-json\/wp\/v2\/research_team?post=12497"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}