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癌症相关突变在诱导多能干细胞和原始态多能干细胞中被鉴定。

Cancer-Related Mutations Identified in Primed and Naive Human Pluripotent Stem Cells.

机构信息

The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus - Givat Ram, Jerusalem, Israel, 9190401.

Department of Stem Cell and Regenerative Biology, and The Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

出版信息

Cell Stem Cell. 2019 Oct 3;25(4):456-461. doi: 10.1016/j.stem.2019.09.001. Epub 2019 Sep 19.

Abstract

Human pluripotent stem cells (hPSCs) are known to harbor chromosomal aberrations, affecting their tumorigenic potential. We established a strategy to identify cancer-related point mutations in hPSCs, detecting recurrent mutations in over 20 genes, alongside those previously detected in p53. Importantly, naive hPSCs harbor, on average, four times more mutations than their primed counterparts, which appear primarily in pathways inhibited during naive conversion. Such cancer-related mutations should be taken into consideration in future applications, especially in clinical contexts.

摘要

人类多能干细胞 (hPSCs) 已知存在染色体异常,影响其致瘤潜能。我们建立了一种鉴定 hPSCs 中与癌症相关的点突变的策略,检测到 20 多个基因中存在反复突变,其中一些与之前在 p53 中检测到的突变相同。重要的是,naive hPSCs 平均携带的突变是其 primed 对应物的四倍,这些突变主要出现在 naive 转化过程中被抑制的途径中。在未来的应用中,特别是在临床环境中,应该考虑到这些与癌症相关的突变。

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