nature文章：分化细胞直接形成功能性神经元

饶冠华

分化细胞直接形成功能性神经元（Nerve cells direct）
( L" x+ V" R) x  Y8 Q5 \% A3 o+ d* X4 mDirect conversion of fibroblasts to functional neurons by defined factors% s$ o5 `4 q  e1 N; l5 C
研究发现，成纤维细胞等分化细胞可被重新编程而具有多能性，产生iPS细胞（即诱导多能干细胞）。该发现引起人们很大兴趣，因为它们有潜在治疗用途。现在，Vierbuchen等人发现，利用与用来产生iPS细胞的转录因子截然不同的转录因子的一个鸡尾酒组合，可以对成熟的分化细胞进行引导，在试管中形成功能性神经元，而不需将成纤维细胞逆转到某种胚胎状态。仅仅三个因子，即Ascl1、 Brn2 (Pou3f2) 和Myt1l，就足以将小鼠胚胎成纤维细胞和出生后成纤维细胞转化成功能性神经元。（Article p. 1035; News & Views）
' l/ a2 v' _6 I) Y) o& J, `Nature. 2010 Jan 27. [Epub ahead of print]  f6 S6 w1 f; g. z* n' I

3 [' u5 b0 k- w# P% Z4 xDirect conversion of fibroblasts to functional neurons by defined factors.
& d1 w. Z- q8 W/ aVierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M.
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! Q$ ]  ]" A8 Y0 w[1] Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, [2] Program in Cancer Biology.. q9 Z& w" ]0 G, C

+ R8 V+ n( ], BCellular 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.
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( z) C. k; F9 g0 Q( w5 z. @PMID: 20107439 [PubMed - as supplied by publisher]
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: ^$ M& F0 o$ q& A3 _Direct conversion of fibroblasts to functional neurons by defined factors

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