Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells
Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells
复制标题
DOI：
10.1038/emboj.2012.110
复制
发表时间：
2012-06-13
期刊：
影响因子：
11.4
通讯作者：
Rajewsky, Nikolaus
中科院分区：
文献类型：
--
作者：
Oenal, Pinar;Gruen, Dominic;Rajewsky, Nikolaus
淡水真涡虫具有极端的再生能力，由成年动物中丰富的多能干细胞（新成细胞）介导。虽然涡虫出现作为一个有吸引力的干细胞生物学的体内模型系统，在neoblasts的基因表达尚未得到全面剖析，它是未知的，如何在neoblasts的多能性的分子机制与哺乳动物胚胎干细胞（ESC）。我们纯化neoblasts和定量的mRNA和蛋白质表达的测序和鸟枪蛋白质组学。我们鉴定了4000个在新生儿中特异性表达的基因，包括30个已知的新生儿标记物。对于ESC中的多能性重要的基因，包括调控因子以及OCT 4的靶基因，在新成细胞中被很好地保守和上调。我们发现保守的表观遗传调节因子的表达，并通过敲除实验证明了它们对真涡虫再生的要求。生殖细胞特有的转录后调控基因也在neoblast中富集，表明生殖细胞和ESCs存在共同的祖先状态。我们的结论是，多能性的分子决定因素是保守的整个进化和涡虫是人类干细胞生物学的信息模型系统。The EMBO Journal（2012）31，2755-2769. doi：10.1038/daj.2012.110;在线发布2012年4月27日主题分类：发展;基因组学和计算生物学
Freshwater planaria possess extreme regeneration capabilities mediated by abundant, pluripotent stem cells (neoblasts) in adult animals. Although planaria emerged as an attractive in vivo model system for stem cell biology, gene expression in neoblasts has not been profiled comprehensively and it is unknown how molecular mechanisms for pluripotency in neoblasts relate to those in mammalian embryonic stem cells (ESCs). We purified neoblasts and quantified mRNA and protein expression by sequencing and shotgun proteomics. We identified similar to 4000 genes specifically expressed in neoblasts, including all similar to 30 known neoblast markers. Genes important for pluripotency in ESCs, including regulators as well as targets of OCT4, were well conserved and upregulated in neoblasts. We found conserved expression of epigenetic regulators and demonstrated their requirement for planarian regeneration by knockdown experiments. Post-transcriptional regulatory genes characteristic for germ cells were also enriched in neoblasts, suggesting the existence of a common ancestral state of germ cells and ESCs. We conclude that molecular determinants of pluripotency are conserved throughout evolution and that planaria are an informative model system for human stem cell biology. The EMBO Journal (2012) 31, 2755-2769. doi:10.1038/emboj.2012.110; Published online 27 April 2012 Subject Categories: development; genomic & computational biology