通過利用不同轉(zhuǎn)錄因子對(duì)分化的成年細(xì)胞重新編程而產(chǎn)生的“誘導(dǎo)多能干”(iPS)細(xì)胞,,具有“體細(xì)胞核轉(zhuǎn)移”(SCNT)所產(chǎn)生的“胚胎干”(ES)細(xì)胞和來自自然受精的胚胎的ES細(xì)胞的很多典型性質(zhì),。
然而,這三個(gè)細(xì)胞類型并不是相同的,,現(xiàn)在它們之間一個(gè)有趣的差別已被發(fā)現(xiàn):iPS細(xì)胞保留它們來自其中的供體組織的一個(gè)“外成記憶”,,而基于SCNT的重新編程則將成年細(xì)胞的DNA甲基化狀態(tài)重置為接近與ES細(xì)胞相似的狀態(tài)。
在另一項(xiàng)獨(dú)立的研究中,,Ji等人研究了特定DNA甲基化標(biāo)記在特定細(xì)胞系的發(fā)育進(jìn)程中所起作用,。他們對(duì)造血細(xì)胞群進(jìn)行了全基因組DNA甲基化分析,結(jié)果顯示了顯著的外成彈性,。DNA甲基化所發(fā)生的變化,,也許是作為指導(dǎo)命運(yùn)選擇(如:是致力于骨髓發(fā)育,,還是致力于淋巴發(fā)育)的一個(gè)主要因素而出現(xiàn)的。
生物谷推薦原文出處:
Nature doi:10.1038/nature09342
Epigenetic memory in induced pluripotent stem cells
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
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.