Publication Date:
2011-07-05
Description:
Transplantation of dopaminergic neurons can potentially improve the clinical outcome of Parkinson's disease, a neurological disorder resulting from degeneration of mesencephalic dopaminergic neurons. In particular, transplantation of embryonic-stem-cell-derived dopaminergic neurons has been shown to be efficient in restoring motor symptoms in conditions of dopamine deficiency. However, the use of pluripotent-derived cells might lead to the development of tumours if not properly controlled. Here we identified a minimal set of three transcription factors--Mash1 (also known as Ascl1), Nurr1 (also known as Nr4a2) and Lmx1a--that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic (iDA) cells release dopamine and show spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The three factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson's disease patients. Direct generation of iDA cells from somatic cells might have significant implications for understanding critical processes for neuronal development, in vitro disease modelling and cell replacement therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caiazzo, Massimiliano -- Dell'Anno, Maria Teresa -- Dvoretskova, Elena -- Lazarevic, Dejan -- Taverna, Stefano -- Leo, Damiana -- Sotnikova, Tatyana D -- Menegon, Andrea -- Roncaglia, Paola -- Colciago, Giorgia -- Russo, Giovanni -- Carninci, Piero -- Pezzoli, Gianni -- Gainetdinov, Raul R -- Gustincich, Stefano -- Dityatev, Alexander -- Broccoli, Vania -- GTB07001/Telethon/Italy -- England -- Nature. 2011 Jul 3;476(7359):224-7. doi: 10.1038/nature10284.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21725324" target="_blank"〉PubMed〈/a〉
Keywords:
Action Potentials
;
Animals
;
Animals, Newborn
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
*Cell Differentiation/genetics/physiology
;
Cells, Cultured
;
*Cellular Reprogramming/genetics/physiology
;
Dopamine/*metabolism/secretion
;
Embryo, Mammalian/cytology
;
Fibroblasts/*cytology/metabolism
;
Gene Expression Profiling
;
Homeodomain Proteins/genetics/metabolism
;
Humans
;
LIM-Homeodomain Proteins
;
Mice
;
Neurons/*cytology/*metabolism/secretion
;
Nuclear Receptor Subfamily 4, Group A, Member 2/genetics/metabolism
;
Oligonucleotide Array Sequence Analysis
;
Parkinson Disease/pathology
;
Patch-Clamp Techniques
;
Regenerative Medicine
;
Skin/cytology
;
Transcription Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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