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Proc Natl Acad Sci U S A. 2011 Apr 26. [Epub ahead of print]
/ @; w3 p6 J1 w1 |" ?' d* n# fDirect reprogramming of mouse fibroblasts to neural progenitors.
- B r& x8 Z. nKim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S." U3 f* U; Y; w2 T {
SourceDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
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4 T+ w& n4 o( i ^( QAbstract
" e) n; L/ P' Z: Y$ I* @The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.
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加拿大的研究人员成功的将鼠成纤维细胞直接重新编程成为神经前体细胞
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* _, L3 O& F" ^2 e m: Q; c摘要翻译：简单而有效的诱导多能性的方法将有可能为细胞治疗和药物开发提供不同类型的分化细胞。然而，从IPS细胞制造合适的细胞将需要体细胞的重编程和随后的再分化。考虑到这一过程十分费力并且耗时，我们考虑是否有一种更方法能够将体细胞直接重编程，转变为另一个胚层的浦西特异性的干或前体细胞，而跳过中间的诱导多能性这一步。我们发现，瞬时转染4个重编程因子 (Oct4, Sox2, Klf4, and c-Myc) 后，通过合适的细胞输入，能够邮箱的将成纤维细胞转分化为有功能的神经干/前体细胞。与诱导得到的神经元相比，转分化的神前体细胞能够进行体外扩增，并且具有产生多种神经元类型和胶质细胞的能力。我们的结果为基于iPS因子的重编程过程提供了新的范例，就是这种方法经过改进后能够成为转分化的综合平台。 |
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发表于 2011-4-28 23:39
