7月20日,,據(jù)英國《獨(dú)立報(bào)》報(bào)道,,兩個美國科研小組宣稱,,他們首次發(fā)現(xiàn),,成人細(xì)胞在被重新編程為誘導(dǎo)多能干細(xì)胞(iPS)的過程中并不會放棄其對原始組織的“記憶”,,在直接使用iPS細(xì)胞分化成移植用人體組織時,可能會產(chǎn)生問題,。
其中一個科研小組來自美國波士頓兒童醫(yī)院,,該小組領(lǐng)導(dǎo)人喬治·戴利表示,iPS細(xì)胞會保留對用來制造它的原初組織(比如皮膚)的“記憶”,,這一新發(fā)現(xiàn)對目前方興未艾的干細(xì)胞臨床和科研提出了挑戰(zhàn),。
干細(xì)胞是未充分分化、具有自我更新和分化潛能的細(xì)胞,??茖W(xué)家認(rèn)為,使用干細(xì)胞,,可以誘導(dǎo)分化出可替換掉人體病變組織的任何組織和細(xì)胞,。另外,科學(xué)家還希望使用干細(xì)胞修改基因突變,,剔除致病基因,,從根本上消除疾病。
基于此,,干細(xì)胞研究廣受關(guān)注,。迄今為止,唯一被證明能夠安全和有效地制造出干細(xì)胞的方式是以存在巨大倫理爭議的胚胎為基礎(chǔ),,通過細(xì)胞核移植或者克隆獲得胚胎干細(xì)胞,。
2007年11月,美日科學(xué)家分別宣布發(fā)現(xiàn)了將普通皮膚細(xì)胞轉(zhuǎn)化為干細(xì)胞的方法,,他們將這樣得到的干細(xì)胞稱為誘導(dǎo)多能干細(xì)胞(iPS),。iPS細(xì)胞具有和胚胎干細(xì)胞類似的功能,卻繞開了胚胎干細(xì)胞研究面臨的倫理和法律等障礙,因此,,在醫(yī)療領(lǐng)域的應(yīng)用前景非常廣闊,。
最新發(fā)現(xiàn)卻表明,這些iPS細(xì)胞并不能像人類胚胎干細(xì)胞一樣起作用,,它們不能完全地通過重新編程回到最原始的胚胎階段,,如果在移植過程中使用這樣獲得的iPS細(xì)胞,將產(chǎn)生一定的問題,。
不過,,戴利也表示,iPS擁有“記憶”是把雙刃劍,。它可讓病人通過利用自身血液iPS細(xì)胞獲取血液細(xì)胞變得更容易,,只有在使用iPS細(xì)胞獲得一些身體組織來治療諸如糖尿病、帕金森病等時,,這種“記憶”才有可能帶來干擾,。
麻省總醫(yī)院科研小組也證實(shí)了iPS細(xì)胞擁有這樣的“記憶”能力,其研究人員康拉德·霍舍得林格在《自然·生物技術(shù)》雜志上稱,,保留對原初組織的記憶會影響iPS細(xì)胞分化為其它細(xì)胞的能力,,但通過讓iPS細(xì)胞不斷分裂的方法,這種“記憶”還是可以消除的,。
生物谷提供索引:Jose M Polo,Susanna Liu,Maria Eugenia Figueroa,Warakorn Kulalert,Sarah Eminli,Kah Yong Tan,Effie Apostolou,Matthias Stadtfeld,Yushan Li,Toshi Shioda,Sridaran Natesan,Amy J Wagers,Ari Melnick,Todd Evans& Konrad Hochedlinger.Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.Nature Biotechnology,2010.doi:10.1038/nbt.1667 By Bioon.com
作為2007年最具影響力的科學(xué)事件,,iPS的誕生在干細(xì)胞研究領(lǐng)域激起了巨大波瀾,爾后越來越多的國家躋身于此,,力圖獲得有利競爭態(tài)勢,。兩個美國科研小組這一最新發(fā)現(xiàn),無疑給如日中天的iPS潑了瓢冷水,。正如不能指望一名天天想家的士兵義無反顧地沖鋒陷陣,,若iPS總是“念念不忘”原初組織,何以不負(fù)眾望地堪當(dāng)再生醫(yī)療的大任,?無論這個難題最終能不能解決,、怎樣解決,都說明要用iPS完全取代胚胎干細(xì)胞,,絕沒有想像的那么容易,。(生物谷Bioon.com)
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,I. L. Weissman,A. P. Feinberg& G. Q. Daley
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.