Investigation of molecular indicators related to the degree of pluripotency of iPS cells

iPS细胞多能性程度相关分子指标的研究

• 批准号: 24770224
• 负责人: SUGIURA Mayumi
• 金额: $ 3万
• 依托单位: Nara Women's University (2013)National Institute of Radiological Sciences (2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24770224/
• 关键词: iPS; ヒストンエピジェネティクス; 分化能

Although iPS cells have been generated by various methods, considerable quality variation has been observed. This study aimed at finding the molecular indicators for discriminating the quality of iPSCs. We focused on the histone-epigenetic modifications, and obtained the following results. (1) Acceleration of the histone acetylation was observed only in iPSCs with high developmental potential. (2) TSA-treatment on iPSCs showing low pluripotency elicited a temporary accumulation of histone acetylation, resulting in improving their developmental ability. (3) Analysis of the expression of histone modification-related factors suggested a close correlation between the degree of histone acetylation and the expression level of c-Myc and certain HDAC in iPSCs. Such a close correlation was not observed in ES cells. Gene knockdown experiments showed the HDAC is possible to affect differentiated state of iPSCs. (4) Genome integrity of each iPSC was not direct cause of its developmental potential.

虽然iPS细胞已经通过各种方法产生，但已经观察到相当大的质量变化。本研究旨在寻找鉴别iPSCs质量的分子指标。我们重点研究了组蛋白表观遗传修饰，并获得了以下结果。(1)仅在具有高发育潜力的iPSC中观察到组蛋白乙酰化的加速。(2)对显示低多能性的iPSC进行TSA处理引起组蛋白乙酰化的暂时积累，从而改善其发育能力。(3)对组蛋白修饰相关因子表达的分析表明，组蛋白乙酰化程度与iPSCs中c-Myc和某些HDAC的表达水平密切相关。在ES细胞中没有观察到这种密切的相关性。基因敲低实验表明HDAC可能影响iPSCs的分化状态。(4)每个iPSC的基因组完整性不是其发育潜力的直接原因。

项目成果

A comparison between iPSCs and ESCs reveals that genome reprogramming during iPSC generation causes transversion-predominant point mutations

iPSC 和 ESC 之间的比较表明，iPSC 生成过程中的基因组重编程会导致颠换为主的点突变

• 发表时间: 2012
• 作者: Ryoko Araki;Masahiro Uda;Yuko Hoki-Fujimori;Miki Nakamura;Shunsuke Ando;Misato Sunayama;Mayumi Sugiura;Hisashi Ideno;Akemi Shimada;Akira Nifuji and Masumi Abe;杉浦真由美・笠間康次・藤森ゆう子・宇田昌広・中村美樹・安藤俊輔・砂山美里・荒木良子・安倍真澄
• 通讯作者: 杉浦真由美・笠間康次・藤森ゆう子・宇田昌広・中村美樹・安藤俊輔・砂山美里・荒木良子・安倍真澄

iPS cells generation-associated point mutations

iPS 细胞世代相关的点突变

• 发表时间: 2013
• 作者: 荒木良子;杉浦真由美;笠間康次;砂山美里;宇田昌広;安藤俊輔;中村美樹;法喜ゆう子;安倍真澄
• 通讯作者: 安倍真澄

iPS cells generation-associated point mutations, International Society for Stem Cell

iPS 细胞世代相关点突变，国际干细胞学会

• 发表时间: 2013
• 作者: Ryoko Araki;Mayumi Sugiura;Yasuji Kasama;Misato Sunayama;Masahiro Uda;Miki Nakamura;Shunsuke Ando;Yuko Hoki;Masumi Abe
• 通讯作者: Masumi Abe

Acceleration of the histone acetylation in pluripotent iPS cells

多能 iPS 细胞中组蛋白乙酰化的加速

• 发表时间: 2013
• 作者: 杉浦真由美;法喜ゆう子;砂山美里;宇田昌広;荒木良子;安倍真澄
• 通讯作者: 安倍真澄

Point mutations in ES cells

ES细胞的点突变

• 发表时间: 2013
• 作者: 砂山美里;杉浦真由美;法喜ゆう子;笠間康次;宇田昌広;中村美樹;安藤俊輔;荒木良子;安倍真澄
• 通讯作者: 安倍真澄