Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.
Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.
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DOI：
10.1038/s41467-022-31707-4
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发表时间：
2022-07-26
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
地图状萎缩是老年性黄斑变性的一种晚期形式，目前还没有治疗方法。因此，需要创新的研究来模拟这种情况并预防或延迟其进展。从地图状萎缩患者和健康个体产生的诱导多能干细胞分化为视网膜色素上皮。整合127，659个视网膜色素上皮细胞的转录谱，这些细胞来自43个地图状萎缩患者和36个对照组，基因型数据，我们确定了445个顺式表达的数量性状位点，这些位点与疾病状态相关，并且对视网膜色素上皮亚群具有特异性。转录组学和蛋白质组学方法鉴定地图状萎缩中显著上调的分子途径，包括线粒体功能、代谢途径和细胞外基质重组。五个重要的蛋白质数量性状基因座，调节蛋白质表达的视网膜色素上皮细胞和地图状萎缩被确定-其中两个共享的顺式表达的数量性状基因座的变体，包括蛋白质参与线粒体生物学和神经变性。线粒体代谢的研究证实线粒体功能障碍是地图状萎缩患者视网膜色素上皮的核心组成性差异。这项研究揭示了地图状萎缩相关的视网膜色素上皮细胞稳态的重要差异。视网膜相关性黄斑变性（AMD）是视力丧失的主要原因，并且对于伴有地图状萎缩的AMD没有批准的治疗。在这里，作者使用患者诱导的多能干细胞衍生的视网膜色素上皮的转录组学和蛋白质组学分析来更好地理解疾病机制。
There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy. Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is no approved treatment for AMD with geographic atrophy. Here, the authors used transcriptomic and proteomic analyses of patient induced pluripotent stem cell-derived retinal pigment epithelium to better understand disease mechanisms.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1126/science.1260793
发表时间：
2015-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Battle A;Khan Z;Wang SH;Mitrano A;Ford MJ;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
64.5
作者：
Cowan CS;Renner M;De Gennaro M;Gross-Scherf B;Goldblum D;Hou Y;Munz M;Rodrigues TM;Krol J;Szikra T;Cuttat R;Waldt A;Papasaikas P;Diggelmann R;Patino-Alvarez CP;Galliker P;Spirig SE;Pavlinic D;Gerber-Hollbach N;Schuierer S;Srdanovic A;Balogh M;Panero R;Kusnyerik A;Szabo A;Stadler MB;Orgül S;Picelli S;Hasler PW;Hierlemann A;Scholl HPN;Roma G;Nigsch F;Roska B
通讯作者：
Roska B