Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
Cell Stem Cell. 2016 Sep 1;19(3):341-54. doi: 10.1016/j.stem.2016.06.019. Epub 2016 Jul 28.
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.
诱导多能干细胞（iPSC）向特定谱系分化的能力差异是其在临床应用和疾病建模中应用的一个重大关注点。为了确定影响分化能力的因素，我们使用 35 个人 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之间进行整合分析。我们的分析表明，多能干细胞向造血前体细胞的造血定向与 IGF2 表达水平相关，而 IGF2 表达水平又取决于中胚层基因的信号依赖性染色质可及性。PSC 来源的造血前体细胞向成熟血细胞的成熟转化能力与重编程过程中获得的 DNA 甲基化的量和模式有关。因此，我们的研究深入了解了决定人 iPSC 系之间差异能力的分子特征，并通过该信息的预测潜力，突出了选择用于临床应用的最佳 iPSC 的方法。
