In vivo reprogramming of astrocytes to neuroblasts in the adult brain

被引:371
作者
Niu, Wenze [1 ]
Zang, Tong [1 ]
Zou, Yuhua [1 ]
Fang, Sanhua [1 ,2 ,3 ]
Smith, Derek K. [1 ]
Bachoo, Robert [4 ]
Zhang, Chun-Li [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310058, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sch Med, Inst Neurosci, Hangzhou 310058, Zhejiang, Peoples R China
[4] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA
关键词
NEURAL STEM-CELLS; DIRECT CONVERSION; NEUROTROPHIC FACTOR; HUMAN FIBROBLASTS; NEURONAL DEVELOPMENT; FUNCTIONAL-NEURONS; MOUSE FIBROBLASTS; CYSTATIN-C; SOX2; NEUROGENESIS;
D O I
10.1038/ncb2843
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Adult differentiated cells can be reprogrammed into pluripotent stem cells or lineage-restricted proliferating precursors in culture; however, this has not been demonstrated in vivo. Here, we show that the single transcription factor SOX2 is sufficient to reprogram resident astrocytes into proliferative neuroblasts in the adult mouse brain. These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged brains. When supplied with BDNF and noggin or when the mice are treated with a histone deacetylase inhibitor, iANBs develop into electrophysiologically mature neurons, which functionally integrate into the local neural network. Our results demonstrate that adult astrocytes exhibit remarkable plasticity in vivo, a feature that might have important implications in regeneration of the central nervous system using endogenous patient-specific glial cells.
引用
收藏
页码:1164 / U94
页数:23
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