Human Amniotic Epithelial Cells are Reprogrammed More Efficiently by Induced Pluripotency than Adult Fibroblasts
Human Amniotic Epithelial Cells are Reprogrammed More Efficiently by Induced Pluripotency than Adult Fibroblasts
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DOI：
10.1089/cell.2011.0106
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发表时间：
2012-06-01
影响因子：
1.6
通讯作者：
Schatten, Gerald P.
中科院分区：
文献类型：
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作者：
Easley, Charles A.;Miki, Toshio;Schatten, Gerald P.
从成体细胞到胚胎细胞样状态的细胞重编程，称为诱导多能性，已经在几种细胞类型中实现。然而，重新编程人羊膜上皮细胞（hAECs）的能力，一个丰富的细胞来源，来自废弃的胎盘组织，最近才被调查。在这里，我们表明，不仅hAECs容易重编程为诱导多能干细胞（AE-iPSC），而且hAECs重编程速度更快，效率更高，比成人和新生儿体皮肤成纤维细胞。此外，与人包皮成纤维细胞iPSC（HFF 1-iPSC）相比，AE-iPSC表达更高水平的NANOG和OCT 4，并且表达降低水平的与分化相关的基因，包括神经元分化的标志物NEUR 0 D1和S 0X 17。为了阐明hAEC更高重编程效率背后的机制，我们分析了全局DNA甲基化，全局组蛋白乙酰化和线粒体DNA A3243 G点突变。尽管与成人和新生儿皮肤成纤维细胞相比，hAEC在整体组蛋白乙酰化或线粒体点突变积累方面没有显示出差异，但与皮肤成纤维细胞相比，hAEC表现出降低的整体DNA甲基化。同样，定量基因表达分析表明，hAEC内源性表达OCT 4、SOX 2、KLF 4和c-MYC，这四种因子都用于细胞重编程。因此，hAEC代表了用于测试用于产生临床上有活力的iPSC的新方法的理想细胞类型，并且提供了优于更可能被环境暴露和感染因子污染的出生后细胞的显著优势。
Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents.