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增加人类多能干细胞现有品系的遗传混合度。

Increasing The Genetic Admixture of Available Lines of Human Pluripotent Stem Cells.

机构信息

National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, SP 05508-900, Brazil.

Laboratory of Evolutionary Genetics, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, SP 05508-900, Brazil.

出版信息

Sci Rep. 2016 Oct 6;6:34699. doi: 10.1038/srep34699.

Abstract

Human pluripotent stem cells (hPSCs) may significantly improve drug development pipeline, serving as an in vitro system for the identification of novel leads, and for testing drug toxicity. Furthermore, these cells may be used to address the issue of differential drug response, a phenomenon greatly influenced by genetic factors. This application depends on the availability of hPSC lines from populations with diverse ancestries. So far, it has been reported that most lines of hPSCs derived worldwide are of European or East Asian ancestries. We have established 23 lines of hPSCs from Brazilian individuals, and we report the analysis of their genomic ancestry. We show that embryo-derived PSCs are mostly of European descent, while induced PSCs derived from participants of a national-wide Brazilian cohort study present high levels of admixed European, African and Native American genomic ancestry. Additionally, we use high density SNP data and estimate local ancestries, particularly those of CYP genes loci. Such information will be of key importance when interpreting variation among cell lines with respect to cellular phenotypes of interest. The availability of genetically admixed lines of hPSCs will be of relevance when setting up future in vitro studies of drug response.

摘要

人多能干细胞(hPSCs)可以显著改善药物开发管道,作为鉴定新型先导化合物和测试药物毒性的体外系统。此外,这些细胞可用于解决药物反应差异的问题,这种现象受遗传因素的影响很大。这种应用取决于是否有来自不同祖先群体的 hPSC 系。到目前为止,据报道,全世界大多数 hPSC 系都具有欧洲或东亚血统。我们已经从巴西个体中建立了 23 株 hPSC,并报告了它们基因组祖先的分析。我们表明,胚胎衍生的 PSCs 主要来自欧洲血统,而来自全国巴西队列研究参与者的诱导 PSCs 则呈现出高水平的混合欧洲、非洲和美洲原住民基因组祖先。此外,我们还使用高密度 SNP 数据和估计局部祖先,特别是 CYP 基因座的局部祖先。当解释与感兴趣的细胞表型有关的细胞系之间的变异时,这些信息将是至关重要的。当建立未来的药物反应体外研究时,具有遗传混合的 hPSC 系的可用性将具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4954/5052616/8ae34d7d955a/srep34699-f1.jpg

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