Amniotic Fluid Cells Are More Efficiently Reprogrammed to Pluripotency Than Adult Cells
Amniotic Fluid Cells Are More Efficiently Reprogrammed to Pluripotency Than Adult Cells
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DOI：
10.1089/cell.2009.0077
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发表时间：
2010-04-01
影响因子：
1.6
通讯作者：
Polgar, Katalin
中科院分区：
文献类型：
--
作者：
Galende, Elisa;Karakikes, Ioannis;Polgar, Katalin
近年来，体外培养的成人皮肤细胞被重编程为诱导多能干细胞（iPS），这种细胞具有与人胚胎干细胞（hES）相似的特征。患者来源的iPS细胞为细胞和组织替代或工程提供了遗传和免疫方面的优势。产生人类iPS细胞的效率一直很低；因此，一种容易和有效的重编程细胞类型是非常需要的。在这里，我们证明了最终分化的人羊水（AF）皮肤细胞为有效地产生丰度诱导的多能干细胞（AF- ips）提供了一个可获得的来源。通过转录因子四重奏（OCT3/4, SOX2， KLF4和c-MYC）诱导多能性，与培养的成人皮肤细胞相比，最终分化的AF皮肤细胞形成iPS集落的速度约为两倍，数量增加近200%。AF-iPS细胞在形态和生长特征、抗原干细胞标记物、干细胞基因表达、端粒酶活性、体外和体内三种胚层分化以及形成胚状体（EBs）和畸胎瘤的能力方面与hES细胞相同。我们的研究结果提供了一个有趣的生物学结论，即这些胎儿AF细胞比新生儿和成人细胞更快速、更容易、更有效地重编程为多能性。AF-iPS细胞可能具有“年轻”，更像胚胎的表观遗传背景，这可能促进和加速多能性。高效、快速重编程终末分化AF皮肤细胞并产生诱导多能干细胞的能力为各种基础研究提供了丰富的iPS细胞来源，并为未来的患者特异性个性化治疗提供了潜力。
Recently, cultured human adult skin cells were reprogrammed to induced pluripotent stem (iPS) cells, which have characteristics similar to human embryonic stem (hES) cells. Patient-derived iPS cells offer genetic and immunologic advantages for cell and tissue replacement or engineering. The efficiency of generating human iPS cells has been very low; therefore an easily and efficiently reprogrammed cell type is highly desired. Here, we demonstrate that terminally differentiated human amniotic fluid (AF) skin cells provide an accessible source for efficiently generating abundant-induced pluripotent stem (AF-iPS) cells. By induction of pluripotency with the transcription factor quartet (OCT3/4, SOX2, KLF4, and c-MYC) the terminally differentiated, cultured AF skin cells formed iPS colonies approximately twice as fast and yielded nearly a two-hundred percent increase in number, compared to cultured adult skin cells. AF-iPS cells were identical to hES cells for morphological and growth characteristics, antigenic stem cell markers, stem cell gene expression, telomerase activity, in vitro and in vivo differentiation into the three germ layers and for their capacity to form embryoid bodies (EBs) and teratomas. Our findings provide a biological interesting conclusion that these fetal AF cells are more rapidly, easily, and efficiently reprogrammed to pluripotency than neonatal and adult cells. AF-iPS cells may have a "young,'' more embryonic like epigenetic background, which may facilitate and accelerate pluripotency. The ability to efficiently and rapidly reprogram terminally differentiated AF skin cells and generate induced pluripotent stem cells provides an abundant iPS cell source for various basic studies and a potential for future patient-specific personalized therapies.