Loss of RE-1 silencing factor in mesenchymal stem cell-derived dopamine progenitors induces functional maturity

Katarzyna A. Trzaska, Bobby Y. Reddy, Jessian L. Munoz, Ke Yong Li, Jiang Hong Ye, Pranela Rameshwar

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Stem cell-derived dopamine (DA) neurons hold great promise for Parkinson's disease (PD). Mesenchymal stem cells (MSCs) have great potential for clinical applications. The generation of DA cells from MSCs using sonic hedgehog (SHH) and fibroblast growth factors (FGF8 and bFGF) has been reported. However, the DA cells showed weak electrical properties, representing DA neuron progenitors. Since RE-1 Silencing Factor (REST), suppresses mature neuronal genes in neuronal progenitors, we studied its role in the maturation of MSC-derived DA cells. REST expression did not change during the induction process, thus we knocked down REST and subjected MSCs to the same neural induction cocktail. We observed increases in the protein level of the Na+ voltage-gated channel and tyrosine hydroxylase (TH). Electrophysiological analyses showed spontaneous firings and spontaneous postsynaptic currents, similar to native DA neurons. Taken together, these results show REST as the limiting gene in the generation of functional mature neurons from MSCs.

Original languageEnglish (US)
Pages (from-to)285-290
Number of pages6
JournalMolecular and Cellular Neuroscience
Volume39
Issue number2
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Keywords

  • Dopamine
  • Mesenchymal stem cells
  • Neural repair
  • REST/NRSF

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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