Direct Reprogramming of Human Fibroblasts into Dopaminergic Neuron-like Cells

Overview

Journal Cell Res

Specialty Cell Biology

Date 2011 Nov 23

PMID 22105488

Citations 87

Authors

Xinjian Liu

Fang Li

Elizabeth A Stubblefield

Barbara Blanchard

Toni L Richards

Gaynor A Larson

Yujun He

Qian Huang

Aik-Choon Tan

Dabing Zhang

Timothy A Benke

John R Sladek

Nancy R Zahniser

Chuan-Yuan Li

Affiliations

Soon will be listed here.

Abstract

Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1, and Pitx3 can directly and effectively reprogram human fibroblasts into DA neuron-like cells. The reprogrammed cells stained positive for various markers for DA neurons. They also showed characteristic DA uptake and production properties. Moreover, they exhibited DA neuron-specific electrophysiological profiles. Finally, they provided symptomatic relief in a rat PD model. Therefore, our directly reprogrammed DA neuron-like cells are a promising source of cell-replacement therapy for PD.

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