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重编程的小鼠星形胶质细胞保留了组织来源的“记忆”,并且比重编程的小鼠胚胎成纤维细胞具有更多的神经元分化倾向。

Reprogrammed mouse astrocytes retain a "memory" of tissue origin and possess more tendencies for neuronal differentiation than reprogrammed mouse embryonic fibroblasts.

机构信息

Laboratory of Neuroimmunology and Regenerative Therapy, University of Nebraska Medical Center, Omaha, NE 68198-5930, USA.

出版信息

Protein Cell. 2011 Feb;2(2):128-40. doi: 10.1007/s13238-011-1012-7. Epub 2011 Mar 5.

Abstract

Direct reprogramming of a variety of somatic cells with the transcription factors Oct4 (also called Pou5f1), Sox2 with either Klf4 and Myc or Lin28 and Nanog generates the induced pluripotent stem cells (iPSCs) with marker similarity to embryonic stem cells. However, the difference between iPSCs derived from different origins is unclear. In this study, we hypothesized that reprogrammed cells retain a "memory" of their origins and possess additional potential of related tissue differentiation. We reprogrammed primary mouse astrocytes via ectopic retroviral expression of OCT3/4, Sox2, Klf4 and Myc and found the iPSCs from mouse astrocytes expressed stem cell markers and formed teratomas in SCID mice containing derivatives of all three germ layers similar to mouse embryonic stem cells besides semblable morphologies. To test our hypothesis, we compared embryonic bodies (EBs) formation and neuronal differentiation between iPSCs from mouse embryonic fibroblasts (MEFsiPSCs) and iPSCs from mouse astrocytes (mAsiPSCs). We found that mAsiPSCs grew slower and possessed more potential for neuronal differentiation compared to MEFsiPSCs. Our results suggest that mAsiPSCs retain a "memory" of the central nervous system, which confers additional potential upon neuronal differentiation.

摘要

多种体细胞通过转录因子 Oct4(也称为 Pou5f1)、Sox2 与 Klf4 和 Myc 或 Lin28 和 Nanog 的直接重编程产生与胚胎干细胞标记相似的诱导多能干细胞 (iPSC)。然而,不同来源的 iPSC 之间的差异尚不清楚。在这项研究中,我们假设重编程细胞保留其起源的“记忆”,并具有相关组织分化的额外潜力。我们通过异位逆转录病毒表达 OCT3/4、Sox2、Klf4 和 Myc 重编程原代小鼠星形胶质细胞,发现来自小鼠星形胶质细胞的 iPSC 表达干细胞标记物,并在含有三个胚层衍生物的 SCID 小鼠中形成畸胎瘤,类似于胚胎干细胞除了相似的形态外,还有类似的形态。为了验证我们的假设,我们比较了来自小鼠胚胎成纤维细胞 (MEFsiPSCs) 的 iPSC 和来自小鼠星形胶质细胞 (mAsiPSCs) 的 iPSC 之间的胚胎体 (EB) 形成和神经元分化。我们发现 mAsiPSCs 的生长速度较慢,并且具有比 MEFsiPSCs 更高的神经元分化潜力。我们的结果表明 mAsiPSCs 保留了中枢神经系统的“记忆”,这赋予了神经元分化的额外潜力。

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