Selective Generation of Dopaminergic Precursors from Mouse Fibroblasts by Direct Lineage Conversion

• DOI: 10.1038/srep12622
• Publication Date: 2015-07-30T09:14:48Z
• Authors: Changhai Tian; Yuju Li; Yunlong Huang; Yongxiang Wang; Dapeng Chen; Jinxu Liu; Xiaobei Deng; Lijun Sun; Kristi Anderson; Xinrui Qi; Yulong Li; R. Lee Mosley; Xiangmei Chen; Jian Huang; Jialin C. Zheng
• Keywords: Lineage (genetic); Cell lineage

Degeneration of midbrain dopaminergic (DA) neurons is a key pathological event Parkinson's disease (PD). Limited adult neurogenesis has led to novel therapeutic strategies such as transplantation precursors (DPs). However, this strategy currently restrained by lack cell source, the tendency for DPs become glial-restricted state, and tumor formation after transplantation. Here, we demonstrate direct conversion mouse fibroblasts into induced (iDPs) ectopic expression Brn2, Sox2 Foxa2. Besides with neural progenitor markers genes including Corin, Otx2 Lmx1a, iDPs were restricted neuronal lineage upon differentiation. After MPTP-lesioned mice, differentiated DA neurons, functionally alleviated motor deficits, reduced loss striatal axonal termini. Importantly, no iDPs-derived astrocytes neoplasia detected in brains We propose that from reprogramming provides safe efficient source PD treatment.