Nature：三种干细胞类型之间的差别（附原文）

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通过利用不同转录因子对分化的成年细胞重新编程而产生的“诱导多能干”(iPS)细胞，具有“体细胞核转移”(SCNT)所产生的“胚胎干”(ES)细胞和来自自然受精的胚胎的ES细胞的很多典型性质。
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然而，这三个细胞类型并不是相同的，现在它们之间一个有趣的差别已被发现：iPS细胞保留它们来自其中的供体组织的一个“外成记忆”，而基于SCNT的重新编程则将成年细胞的DNA甲基化状态重置为接近与ES细胞相似的状态。0 [* ?# ~6 T$ i! ]# n# P" D8 M

" z6 u+ z1 G- ?在另一项独立的研究中，Ji等人研究了特定DNA甲基化标记在特定细胞系的发育进程中所起作用。他们对造血细胞群进行了全基因组DNA甲基化分析，结果显示了显著的外成弹性。DNA甲基化所发生的变化，也许是作为指导命运选择（如：是致力于骨髓发育，还是致力于淋巴发育）的一个主要因素而出现的。" E6 }' s- O( g

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. O% H  X" X+ ZNature doi:10.1038/nature09342
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Epigenetic memory in induced pluripotent stem cells& K; i7 q! |, _9 y" `* ~/ U
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K. Kim,A. Doi,B. Wen,K. Ng,R. Zhao,P. Cahan,J. Kim,M. J. Aryee,H. Ji,L. I. R. Ehrlich,A. Yabuuchi,A. Takeuchi,K. C. Cunniff,H. Hongguang,S. Mckinney-Freeman,O. Naveiras,T. J. Yoon,R. A. Irizarry,N. Jung,J. Seita,J. Hanna,P. Murakami,R. Jaenisch,R. Weissleder,S. H. Orkin
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9 v' Z# u' `+ _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. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours 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 iPSCs 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 iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.4 n" H; K# w/ H4 i

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2楼原文 感谢flydayzhu提供

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回复 2# flydayzhu
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    感谢提供原文！

ydj19830

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   “差异随着 iPS 细胞长期培养而逐渐减少,  iPS 细胞更接近 ES 细胞’，我对这句话很感兴趣，很可能是细胞分裂导致原代细胞本身含有的某些标记被逐渐稀释的缘故？还请指教。