Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells

Research output: Contribution to journalArticle

Abstract

Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.

Details

Authors
  • Stina Friling
  • Elisabet Andersson
  • Lachlan Thompson
  • Marie Jönsson
  • Josephine Hebsgaard
  • Evanthia Nanou
  • Zhanna Alekseenko
  • Ulrika Marklund
  • Susanna Kjellander
  • Nikolaos Volakakis
  • Outi Hovatta
  • Abdeljabbar El Manira
  • Anders Björklund
  • Thomas Perlmann
  • Johan Ericson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Parkinson, neuroscience, intrinsic determinant, magnetic bead sorting, disease, transplantation
Original languageEnglish
Pages (from-to)7613-7618
JournalProceedings of the National Academy of Sciences
Volume106
Issue number18
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes