首页> 美国卫生研究院文献>International Journal of Biological Sciences >Direct Reprogramming of Human Amniotic Fluid Stem Cells by OCT4 and Application in Repairing of Cerebral Ischemia Damage
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Direct Reprogramming of Human Amniotic Fluid Stem Cells by OCT4 and Application in Repairing of Cerebral Ischemia Damage

机译:OCT4直接重编程人羊水干细胞及其在脑缺血损伤修复中的应用

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摘要

Amniotic fluid stem cells (AFSCs) are a type of fetal stem cell whose stemness encompasses both embryonic and adult stem cells, suggesting that they may be easily and efficiently reprogrammed into induced pluripotent stem cells (iPSCs). To further simplify the reprogramming process, the creation of AFSC-derived iPSCs using a single factor is desirable. Here we report the generation of one-factor human AFSC-iPSCs (AiPSCs) from human AFSCs by ectopic expression of the transcription factor OCT4. Just like human embryonic stem cells, AiPSCs exhibited similar epigenetic status, global gene expression profiles, teratoma formation and in vitro & in vivo pluripotency. Our results indicate that the OCT4 is necessary and sufficient to directly reprogram human AFSCs into pluripotent AiPSCs. Moreover, reflecting the similar memory characteristics of AFSCs and neural stem cells, we show that AiPSC membrane-derived vesicles (MVs) repair cerebral ischemia damage. We anticipate that the successful generation of one-factor AiPSCs will facilitate the creation of patient-specific pluripotent stem cells without the need for transgenic expression of oncogenes. Moreover, MVs from tissue-specific AiPSCs have potential in tissue repair, representing a novel application of iPSCs.
机译:羊水干细胞(AFSC)是一种胎儿干细胞,其干细胞既包括胚胎干细胞也包括成年干细胞,这表明它们可以轻松,有效地重编程为诱导性多能干细胞(iPSC)。为了进一步简化重新编程过程,需要使用单个因素来创建AFSC衍生的iPSC。在这里,我们报告通过转录因子OCT4的异位表达从人AFSC中生成单因素人AFSC-iPSC(AiPSC)。就像人类胚胎干细胞一样,AiPSC表现出相似的表观遗传状态,整体基因表达谱,畸胎瘤形成以及体外和体内多能性。我们的结果表明,OCT4是将人类AFSC直接重编程为多能AiPSC的必要和充分条件。此外,反映AFSCs和神经干细胞的相似的记忆特征,我们表明AiPSC膜衍生的囊泡(MVs)修复脑缺血损伤。我们预计,单因子AiPSC的成功产生将有助于创建患者特异性多能干细胞,而无需致癌基因的转基因表达。此外,来自组织特异性AiPSC的MV在组织修复中具有潜力,代表了iPSC的新应用。

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