Common genetic variation drives molecular heterogeneity in human iPSCs.
Common genetic variation drives molecular heterogeneity in human iPSCs.
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DOI：
10.1038/nature22403
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发表时间：
2017-06-15
期刊：
影响因子：
64.8
通讯作者：
Gaffney DJ
中科院分区：
文献类型：
--
作者：
Kilpinen H;Goncalves A;Leha A;Afzal V;Alasoo K;Ashford S;Bala S;Bensaddek D;Casale FP;Culley OJ;Danecek P;Faulconbridge A;Harrison PW;Kathuria A;McCarthy D;McCarthy SA;Meleckyte R;Memari Y;Moens N;Soares F;Mann A;Streeter I;Agu CA;Alderton A;Nelson R;Harper S;Patel M;White A;Patel SR;Clarke L;Halai R;Kirton CM;Kolb-Kokocinski A;Beales P;Birney E;Danovi D;Lamond AI;Ouwehand WH;Vallier L;Watt FM;Durbin R;Stegle O;Gaffney DJ
诱导多能干细胞(IPSC)技术在提供改进的人类疾病细胞模型方面具有巨大的潜力。然而，许多现有IPSC株系的可变遗传和表型特征限制了它们在研究和治疗方面的潜在用途。在这里，我们描述了由人类诱导多能干细胞倡议(HipSci：http://www.hipsci.org).)从30 1名健康个体获得的711个IPSC系的系统产生、基因分型和表型我们的研究概述了IPSCs遗传和表型变异的主要来源，并建立了它们作为复杂人类特征和癌症模型的适用性。通过全基因组图谱我们发现，包括分化能力和细胞形态在内的不同IPSC表型的5%-46%的变异源于个体之间的差异。此外，我们评估了在IPSC重新编程中反复观察到的罕见的基因组拷贝数突变的表型后果，并提供了影响人类多能细胞转录组的常见调控变量的全面图谱。
Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.6
作者：
Cordell HJ;Han Y;Mells GF;Li Y;Hirschfield GM;Greene CS;Xie G;Juran BD;Zhu D;Qian DC;Floyd JA;Morley KI;Prati D;Lleo A;Cusi D;Canadian-US PBC Consortium;Italian PBC Genetics Study Group;UK-PBC Consortium;Gershwin ME;Anderson CA;Lazaridis KN;Invernizzi P;Seldin MF;Sandford RN;Amos CI;Siminovitch KA
通讯作者：
Siminovitch KA
影响因子：
30.8
作者：
Bentham J;Morris DL;Graham DSC;Pinder CL;Tombleson P;Behrens TW;Martín J;Fairfax BP;Knight JC;Chen L;Replogle J;Syvänen AC;Rönnblom L;Graham RR;Wither JE;Rioux JD;Alarcón-Riquelme ME;Vyse TJ
通讯作者：
Vyse TJ
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
5.8
作者：
Aryee, Martin J.;Jaffe, Andrew E.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.