iPS細(xì)胞(誘導(dǎo)多能干細(xì)胞)在多大程度上相當(dāng)于胚胎干細(xì)胞(ES細(xì)胞)是一個(gè)并沒(méi)有惟一答案的問(wèn)題。一些研究報(bào)告稱,,與ES細(xì)胞相比,,數(shù)百個(gè)基因在iPS細(xì)胞中異常表達(dá),而iPS細(xì)胞能夠通過(guò)四倍體胚胎互補(bǔ)生成全為iPS細(xì)胞的小鼠來(lái)滿足關(guān)于發(fā)育潛力的最為嚴(yán)格的測(cè)試之一,。
為了用最少量的涉及因子來(lái)回答這一問(wèn)題,,Stadtfeld等人對(duì)在遺傳上相同的小鼠ES 和 iPS細(xì)胞中的基因表達(dá)進(jìn)行了比較。他們發(fā)現(xiàn),,mRNA 和 microRNA總體表達(dá)模式是無(wú)法區(qū)分的,,少數(shù)轉(zhuǎn)錄體和少于20個(gè)由12qF1染色體上一個(gè)印記基因簇編碼的microRNA除外。iPS細(xì)胞的發(fā)育潛力取決于基因在這個(gè)點(diǎn)上是被關(guān)閉(沉默)還是處于活躍狀態(tài),。(生物谷Bioon.com)
更多閱讀
Biol.Reprod.:iPS 細(xì)胞中利用核移植獲克隆小鼠
Nature:iPS細(xì)胞分化發(fā)育能力低于胚胎干細(xì)胞
Nature:iPS細(xì)胞轉(zhuǎn)化率提高約百倍
Nature:iPS細(xì)胞分化發(fā)育能力低于胚胎干細(xì)胞
Cell:胚胎干細(xì)胞自我更新與分化平衡維持機(jī)制
SCD:利用人類胚胎干細(xì)胞造出人造精子
生物谷推薦原文出處:
Nature doi:10.1038/nature09017
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells
Matthias Stadtfeld,Effie Apostolou,Hidenori Akutsu,Atsushi Fukuda,Patricia Follett,Sridaran Natesan,Tomohiro Kono,Toshi Shioda& Konrad Hochedlinger
Induced pluripotent stem cells (iPSCs) have been generated by enforced expression of defined sets of transcription factors in somatic cells. It remains controversial whether iPSCs are molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells. By comparing genetically identical mouse ES cells and iPSCs, we show here that their overall messenger RNA and microRNA expression patterns are indistinguishable with the exception of a few transcripts encoded within the imprinted Dlk1–Dio3 gene cluster on chromosome 12qF1, which were aberrantly silenced in most of the iPSC clones. Consistent with a developmental role of the Dlk1–Dio3 gene cluster, these iPSC clones contributed poorly to chimaeras and failed to support the development of entirely iPSC-derived animals (‘all-iPSC mice’). In contrast, iPSC clones with normal expression of the Dlk1–Dio3 cluster contributed to high-grade chimaeras and generated viable all-iPSC mice. Notably, treatment of an iPSC clone that had silenced Dlk1–Dio3 with a histone deacetylase inhibitor reactivated the locus and rescued its ability to support full-term development of all-iPSC mice. Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells.