Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes.
Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes.
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祖先依赖性基因表达与重编程与多能性和多种动态生物学过程相关。
DOI：
10.1126/sciadv.abc3851
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发表时间：
2020-11
期刊：
影响因子：
13.6
通讯作者：
Archer TK
中科院分区：
文献类型：
--
作者：
Bisogno LS;Yang J;Bennett BD;Ward JM;Mackey LC;Annab LA;Bushel PR;Singhal S;Schurman SH;Byun JS;Nápoles AM;Pérez-Stable EJ;Fargo DC;Gardner K;Archer TK
不同种族的成纤维细胞和iPSC的转录组学分析表明，个体差异性影响多能潜能。诱导多能干细胞（iPSC）可以来源于分化的细胞，使得能够通过将患者来源的iPSC分化成疾病相关的细胞系来生成个性化的疾病模型。虽然不同iPSC系之间的遗传变异性影响分化潜能，但体细胞中的这种变异性如何影响多能潜能尚不清楚。我们生成并比较了72个真皮成纤维细胞-iPSC对的转录组数据，这些数据在重编程效率方面具有一致的变化。通过考虑来自自我报告的非裔美国人和白色美国人的相同数量的样本，我们确定了与重编程效率相关的祖先依赖性和祖先独立性转录本，这表明转录组异质性可以显著影响重编程。此外，重编程效率相关基因参与了多种动态生物学过程，包括癌症和伤口愈合，并且在独立队列中预测了5年乳腺癌生存率。候选基因可以提供对细胞命运转变的祖先依赖性调节机制的深入了解，并激发进一步的研究以改善重编程。
Transcriptomic analysis of racially diverse fibroblasts and iPSCs shows that individual variability affects pluripotent potential. Induced pluripotent stem cells (iPSCs) can be derived from differentiated cells, enabling the generation of personalized disease models by differentiating patient-derived iPSCs into disease-relevant cell lines. While genetic variability between different iPSC lines affects differentiation potential, how this variability in somatic cells affects pluripotent potential is less understood. We generated and compared transcriptomic data from 72 dermal fibroblast–iPSC pairs with consistent variation in reprogramming efficiency. By considering equal numbers of samples from self-reported African Americans and White Americans, we identified both ancestry-dependent and ancestry-independent transcripts associated with reprogramming efficiency, suggesting that transcriptomic heterogeneity can substantially affect reprogramming. Moreover, reprogramming efficiency–associated genes are involved in diverse dynamic biological processes, including cancer and wound healing, and are predictive of 5-year breast cancer survival in an independent cohort. Candidate genes may provide insight into mechanisms of ancestry-dependent regulation of cell fate transitions and motivate additional studies for improvement of reprogramming.
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影响因子：
1.2
作者：
Chi, Lijun;Delgado-Olguin, Paul
通讯作者：
Delgado-Olguin, Paul
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
4.8
作者：
Kinyamu, H. Karimi;Bennett, Brian D.;Archer, Trevor K.
通讯作者：
Archer, Trevor K.
影响因子：
1.2
作者：
Gao, Xiugong;Yourick, Jeffrey J.;Sprando, Robert L.
通讯作者：
Sprando, Robert L.
影响因子：
21.3
作者：
Li M;Izpisua Belmonte JC
通讯作者：
Izpisua Belmonte JC