本帖最后由 细胞海洋 于 2010-1-29 13:23 编辑 3 C; @' _$ [! m% h) e, d: m4 R* l/ J! Z9 Y6 E/ n4 Y
Nature advance online publication 27 January 2010 | doi:10.1038/nature08797! q, p8 `$ M* [* I$ k
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Direct conversion of fibroblasts to functional neurons by defined factors* P7 \% ]- c8 G5 c* D! M9 c
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Thomas Vierbuchen1,2, Austin Ostermeier1,2, Zhiping P. Pang3, Yuko Kokubu1, Thomas C. Südhof3,4 & Marius Wernig1,2( H+ D- x6 |" | t/ c
( K7 I) l( @% K1 Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology,, u i% `. k: b. I
epartment of Molecular and Cellular Physiology,' z, P4 ]) Z+ r. ~6 t; K0 I9 v
2 Howard Hughes Medical Institute, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA - l- z; c5 R+ w" R" Y5 s3 Correspondence to: Marius Wernig1,2 Correspondence and requests for materials should be addressed to M.W.0 ?& Q* `# P8 F* _3 H
8 k2 L0 n' q0 o) HCellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.% C$ v4 \9 N/ I) G% U
; K0 C' y, Y# n5 D8 S& ~2 w6楼原文 感谢版主qizhi502 提供作者: ghfvcat 时间: 2010-1-28 17:28
美国斯坦福大学医学院研究人员27日宣布，他们在实验中绕过诱导多功能干细胞(iPS)这一步骤，首次直接将实验鼠皮肤细胞转化为神经细胞。这项成果对理解细胞分化及再生医学研究均具有重要意义。 w* L( |3 O9 v" p
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研究人员首先选择了19个与细胞重组或神经发展有关的基因，然后利用慢病毒将这些基因植入来自实验鼠胚胎的皮肤细胞中。32天后，其中一些皮肤细胞开始向神经细胞转化。研究人员随后筛选出3个基因，并再次利用慢病毒将其植入来自成年实验鼠尾部的皮肤细胞。一周内，约20％的实验鼠皮肤细胞转化为神经细胞。这些神经细胞不但可以表达神经蛋白，而且可与实验室中的其他神经细胞形成突触。: t! F/ V9 ~# b1 M