Epigenetic Variation between Human Induced Pluripotent Stem Cell Lines Is an Indicator of Differentiation Capacity
Epigenetic Variation between Human Induced Pluripotent Stem Cell Lines Is an Indicator of Differentiation Capacity
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DOI：
10.1016/j.stem.2016.06.019
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发表时间：
2016-09-01
期刊：
影响因子：
23.9
通讯作者：
Yoshida, Yoshinori
中科院分区：
文献类型：
--
作者：
Nishizawa, Masatoshi;Chonabayashi, Kazuhisa;Yoshida, Yoshinori
诱导多能干细胞（iPSCs）向特定谱系分化能力的变化是其在临床应用和疾病建模中的重要关注点。为了确定影响分化能力的因素，我们使用35个人类iPSC系和4个ESC系，对造血分化性能与基因表达、DNA甲基化和染色质状态等分子特征进行了整合分析。我们的分析显示，造血干细胞对造血前体的造血承诺与IGF2表达水平相关，而IGF2表达水平反过来又取决于中胚层基因的信号依赖性染色质可及性。psc衍生的造血前体转化为成熟血液的成熟能力与重编程过程中获得的DNA甲基化的数量和模式有关。因此，我们的研究提供了决定人类iPSC系之间差异能力的分子特征的见解，并通过该信息的预测潜力，强调了为临床应用选择最佳iPSC的方法。
Variation in the differentiation capacity of induced pluripotent stem cells (iPSCs) to specific lineages is a significant concern for their use in clinical applications and disease modeling. To identify factors that affect differentiation capacity, we performed integration analyses between hematopoietic differentiation performance and molecular signatures such as gene expression, DNA methylation, and chromatin status, using 35 human iPSC lines and four ESC lines. Our analyses revealed that hematopoietic commitment of PSCs to hematopoietic precursors correlates with IGF2 expression level, which in turn depends on signaling-dependent chromatin accessibility at mesendodermal genes. Maturation capacity for conversion of PSC-derived hematopoietic precursors to mature blood associates with the amount and pattern of DNA methylation acquired during reprogramming. Our study therefore provides insight into the molecular features that determine the differential capacities seen among human iPSC lines and, through the predictive potential of this information, highlights a way to select optimal iPSCs for clinical applications.