通过对人类多能干细胞的大规模分析揭示的分化缺陷表型。
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
机构信息
Center for iPS Cell Research and Application, Department of Biological Repair, Institute for Frontier Medical Sciences, and Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.
出版信息
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20569-74. doi: 10.1073/pnas.1319061110. Epub 2013 Nov 20.
Abstract
We examined the gene expression and DNA methylation of 49 human induced pluripotent stem cells (hiPSCs) and 10 human embryonic stem cells and found overlapped variations in gene expression and DNA methylation in the two types of human pluripotent stem cell lines. Comparisons of the in vitro neural differentiation of 40 hiPSCs and 10 human embryonic stem cells showed that seven hiPSC clones retained a significant number of undifferentiated cells even after neural differentiation culture and formed teratoma when transplanted into mouse brains. These differentiation-defective hiPSC clones were marked by higher expression levels of several genes, including those expressed from long terminal repeats of specific human endogenous retroviruses. These data demonstrated a subset of hiPSC lines that have aberrant gene expression and defective potential in neural differentiation, which need to be identified and eliminated before applications in regenerative medicine.
摘要
我们检测了 49 个人诱导多能干细胞 (hiPSC) 和 10 个人胚胎干细胞的基因表达和 DNA 甲基化情况，发现这两种人类多能干细胞系的基因表达和 DNA 甲基化存在重叠的变化。对 40 个人诱导多能干细胞和 10 个人胚胎干细胞的体外神经分化比较显示，即使在神经分化培养后，7 个人诱导多能干细胞克隆仍保留了大量未分化细胞，并在移植到小鼠大脑中时形成畸胎瘤。这些分化缺陷的 hiPSC 克隆的特征是，包括来自特定人类内源性逆转录病毒的长末端重复序列表达的几个基因的表达水平较高。这些数据表明，hiPSC 系存在一部分基因表达异常和神经分化缺陷的情况，在再生医学应用之前需要进行鉴定和消除。
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