Epigenetic memory in induced pluripotent stem cells.
Epigenetic memory in induced pluripotent stem cells.
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体细胞核移植和基于转录因子的重编程将成年细胞恢复到胚胎状态，并产生能够生成所有组织的多能干细胞。这两种重编程方法通过不同的机制和动力学重置基因组甲基化，这是一种影响基因表达的DNA的表观遗传修饰，导致我们假设由此产生的多能干细胞可能具有不同的特性。在这里，我们观察到，通过基于因子的重编程获得的低传代诱导多能干细胞(IPSC)具有其起源的体细胞组织特有的残留DNA甲基化特征，这有利于它们沿着与供体细胞相关的谱系分化，同时限制了可供选择的细胞命运。供体组织的这种“表观遗传记忆”可以通过分化和连续重编程来重置，或者通过用染色质修饰药物治疗IPSC来重置。相比之下，核移植衍生的多能干细胞的分化和甲基化更类似于经典的胚胎干细胞，而不是IPSC，这与更有效的重新编程一致。我们的数据表明，基于因子的重编程可以留下起源组织的表观遗传记忆，这可能会影响定向分化在疾病建模或治疗中的应用。
Somatic cell nuclear transfer and transcription factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. These two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, by different mechanisms and kinetics, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low passage induced pluripotent stem cells (iPSC) derived by factor-based reprogramming harbor residual DNA methylation signatures characteristic of their somatic tissue of origin, which favors their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an “epigenetic memory” of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSC with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSC, consistent with more effective reprogramming. Our data demonstrate that factor-based reprogramming can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modeling or treatment.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
64.5
作者：
CHIU, CP;BLAU, HM
通讯作者：
BLAU, HM
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
9.8
作者：
通讯作者：
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