Title | Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Di Giorgio FPaolo, Carrasco MA, Siao MC, Maniatis T, Eggan K |
Journal | Nat Neurosci |
Volume | 10 |
Issue | 5 |
Pagination | 608-14 |
Date Published | 2007 May |
ISSN | 1097-6256 |
Keywords | Amyotrophic Lateral Sclerosis, Analysis of Variance, Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Coculture Techniques, Disease Models, Animal, Embryo, Mammalian, Flow Cytometry, Green Fluorescent Proteins, Humans, Mice, Mice, Transgenic, Motor Neurons, Nerve Tissue Proteins, Neuroglia, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Superoxide Dismutase, Time Factors |
Abstract | Here we report an in vitro model system for studying the molecular and cellular mechanisms that underlie the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation. These motor neurons could be maintained in long-term coculture either with additional cells that arose during differentiation or with primary glial cells. Motor neurons carrying either the nonpathological human SOD1 transgene or the mutant SOD1(G93A) allele showed neurodegenerative properties when cocultured with SOD1(G93A) glial cells. Thus, our studies demonstrate that glial cells carrying a human SOD1(G93A) mutation have a direct, non-cell autonomous effect on motor neuron survival. More generally, our results show that ESC-based models of disease provide a powerful tool for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could provide cell-based assays for the identification of new ALS drugs. |
DOI | 10.1038/nn1885 |
Alternate Journal | Nat. Neurosci. |
PubMed ID | 17435754 |
PubMed Central ID | PMC3139463 |
Grant List | R01 HD046732 / HD / NICHD NIH HHS / United States R01 NS043915 / NS / NINDS NIH HHS / United States R01 NS043915-27 / NS / NINDS NIH HHS / United States R01 HD046732-01A1 / HD / NICHD NIH HHS / United States |
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