Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression.

Published

Journal Article

Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of primary human fibroblasts offer exciting opportunities for treatment of Parkinson's disease. A significant obstacle is the low efficiency of conversion during the reprogramming process. Here, we demonstrate that the suppression of p53 significantly enhances the efficiency of transcription factor-mediated conversion of human fibroblasts into functional dopaminergic neurons. In particular, blocking p53 activity using a dominant-negative p53 (p53-DN) in IMR90 cells increases the conversion efficiency by 5-20 fold. The induced DA neuron-like cells exhibit dopamine neuron-specific gene expression, significant dopamine uptake and production capacities, and enables symptomatic relief in a rat Parkinson's disease model. Taken together, our findings suggest that p53 is a critical barrier in direct reprogramming of fibroblast into dopaminergic neurons.

Full Text

Duke Authors

Cited Authors

  • Liu, X; Huang, Q; Li, F; Li, C-Y

Published Date

  • September 2014

Published In

Volume / Issue

  • 57 / 9

Start / End Page

  • 867 - 875

PubMed ID

  • 25129808

Pubmed Central ID

  • 25129808

Electronic International Standard Serial Number (EISSN)

  • 1869-1889

Digital Object Identifier (DOI)

  • 10.1007/s11427-014-4730-2

Language

  • eng

Conference Location

  • China