iPS细胞(诱导多能干细胞)在多大程度上相当于胚胎干细胞(ES细胞)是一个并没有惟一答案的问题。一些研究报告称,与ES细胞相比,数百个基因在iPS细胞中异常表达,而iPS细胞能够通过四倍体胚胎互补生成全为iPS细胞的小鼠来满足关于发育潜力的最为严格的测试之一。
为了用最少量的涉及因子来回答这一问题,Stadtfeld等人对在遗传上相同的小鼠ES 和 iPS细胞中的基因表达进行了比较。他们发现,mRNA 和 microRNA总体表达模式是无法区分的,少数转录体和少于20个由12qF1染色体上一个印记基因簇编码的microRNA除外。iPS细胞的发育潜力取决于基因在这个点上是被关闭(沉默)还是处于活跃状态。(生物谷Bioon.com)
更多阅读
Biol.Reprod.:iPS 细胞中利用核移植获克隆小鼠
Nature:iPS细胞分化发育能力低于胚胎干细胞
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Nature:iPS细胞分化发育能力低于胚胎干细胞
Cell:胚胎干细胞自我更新与分化平衡维持机制
SCD:利用人类胚胎干细胞造出人造精子
生物谷推荐原文出处:
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.