Direct conversion of fibroblasts to functional neurons by defined factors

被引:2200
作者
Vierbuchen, Thomas [1 ,2 ]
Ostermeier, Austin [1 ,2 ]
Pang, Zhiping P. [3 ]
Kokubu, Yuko [1 ]
Suedhof, Thomas C. [3 ,4 ]
Wernig, Marius [1 ,2 ]
机构
[1] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, Palo Alto, CA 94304 USA
[2] Stanford Univ, Sch Med, Program Canc Biol, Palo Alto, CA 94304 USA
[3] Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Palo Alto, CA 94304 USA
[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Palo Alto, CA 94304 USA
关键词
EMBRYONIC STEM-CELLS; SOMATIC-CELLS; MATURE B; NUCLEAR TRANSFER; PLURIPOTENCY; EXPRESSION; PROTEINS; TRANSPLANTATION; PROGENITORS; GENERATION;
D O I
10.1038/nature08797
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cellular 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.
引用
收藏
页码:1035 / U50
页数:8
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