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Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
- Source :
- Nature; Vol 476, Nature
- Publication Year :
- 2011
- Publisher :
- Nature, 2011.
-
Abstract
- 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.
- Subjects :
- Transcription Factor
Cellular differentiation
Dopamine
Patch-Clamp Technique
Basic Helix-Loop-Helix Transcription Factor
Biology
LIM-Homeodomain Protein
Regenerative Medicine
03 medical and health sciences
Mice
0302 clinical medicine
Settore BIO/13 - Biologia Applicata
Nuclear Receptor Subfamily 4, Group A, Member 2
medicine
Patch clamp
Progenitor cell
Action Potential
Cells, Cultured
030304 developmental biology
Skin
0303 health sciences
Multidisciplinary
Animal
Oligonucleotide Array Sequence Analysi
Gene Expression Profiling
Dopaminergic
Homeodomain Protein
Parkinson Disease
Cell Differentiation
Anatomy
Neuron
Embryo, Mammalian
Cellular Reprogramming
Transplantation
ASCL1
Animals, Newborn
Fibroblast
Stem cell
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Human
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 476
- Issue :
- 7359
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....621e318b8d71b7cc44180bb6f7d6ec7c
- Full Text :
- https://doi.org/10.1038/nature10284