期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 18, 页码 7613-7618出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0902396106
关键词
intrinsic determinant; magnetic bead sorting; neuroscience; Parkinson disease; transplantation
资金
- European Community [222943]
- Knut och Alice Wallenberg Foundation
- Michael J. Fox Foundation for Parkinson's research
- Vetenskapsradet via support to the Linne - Center for Developmental Biology and Regenerative Medicine, Vetenskapsradet
- Goran Gustafssons Stiftelse
- Swedish Foundation for Strategic Research
- Edmond J. Safra Foundation
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.
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