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Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.

机译:将小鼠和人类成纤维细胞直接重编程为单因素多能神经干细胞。

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摘要

Seminal discoveries in the field of cellular reprogramming have demonstrated that human somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells and other somatic cell types such as induced neuronal (iN) cells by ectopically expressing different combinations of defined factors. The impact of these technologies is already being realized with the generation of patient- and disease-specific iPS and iN cells lines. These valuable tools provide new avenues for basic research and potential transplantation therapies for neurological diseases. However, clinical applications must consider the risk of tumor formation by iPS cells upon transplantation and the inability of iN cells to self-renew in culture. Here we report the generation of induced neural stem cells (iNSCs) from mouse and human fibroblasts by direct reprogramming with a single transcription factor, Sox2. iNSCs express neural stem cell (NSC) markers such as Nestin, Sox2, Pax6, and BLBP. They also resemble wild-type NSCs in their morphology, self-renewal, ability to form neurospheres, and gene expression profiles. Cloned iNSCs differentiate into several types of mature neurons, as well as astrocytes and oligodendrocytes, indicating that Sox2 reprogrammed iNSCs are a homogenous population of multipotent NSCs. Implanted iNSCs can survive and integrate in mouse brains and, unlike iPS cell-derived NSCs, do not generate tumors. Thus, self-renewable and multipotent iNSCs without tumorigenic potential can be generated directly from both mouse and human fibroblasts by direct reprogramming.
机译:细胞重编程领域的开创性研究表明,可以通过异位表达定义因子的不同组合,将人体细胞重编程为诱导多能干(iPS)细胞和其他体细胞类型,例如诱导神经元(iN)细胞。这些技术的影响已经随着患者和疾病特定的iPS和iN细胞系的产生而实现。这些有价值的工具为神经疾病的基础研究和潜在的移植疗法提供了新的途径。但是,临床应用必须考虑移植后iPS细胞形成肿瘤的风险以及iN细胞无法在培养中自我更新。在这里,我们报告了通过用单个转录因子Sox2直接重编程从小鼠和人类成纤维细胞中诱导神经干细胞(iNSCs)的产生。 iNSC表达神经干细胞(NSC)标记,例如Nestin,Sox2,Pax6和BLBP。它们的形态,自我更新,形成神经球的能力和基因表达谱也类似于野生型NSC。克隆的iNSC分化成几种类型的成熟神经元,以及星形胶质细胞和少突胶质细胞,这表明Sox2重编程的iNSC是多能NSC的同质群体。植入的iNSC可以存活并整合到小鼠的大脑中,与iPS细胞衍生的NSC不同,它们不会产生肿瘤。因此,可以通过直接重编程直接从小鼠和人成纤维细胞中产生无致瘤性的可自我更新的多能性iNSC。

著录项

  • 作者

    Ring, Karen.;

  • 作者单位

    University of California, San Francisco.;

  • 授予单位 University of California, San Francisco.;
  • 学科 Biology Neuroscience.;Biogeochemistry.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 86 p.
  • 总页数 86
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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