Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation.
It has been proposed that human embryonic stem cells could be used to provide an inexhaustible supply of differentiated cell types for the study of disease processes. Although methods for differentiating embryonic stem cells into specific cell types have become increasingly sophisticated, the utility of the resulting cells for modeling disease has not been determined. We have asked whether specific neuronal subtypes produced from human embryonic stem cells can be used to investigate the mechanisms leading to neural degeneration in amyotrophic lateral sclerosis (ALS). We show that human spinal motor neurons, but not interneurons, are selectively sensitive to the toxic effect of glial cells carrying an ALS-causing mutation in the SOD1 gene. Our findings demonstrate the relevance of these non-cell-autonomous effects to human motor neurons and more broadly demonstrate the utility of human embryonic stem cells for studying disease and identifying potential therapeutics.
Di Giorgio
Francesco Paolo
FP
The Harvard Stem Cell Institute, The Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Cambridge, MA 02138, USA.
Boulting
Gabriella L
GL
Bobrowicz
Samuel
S
Eggan
Kevin C
KC
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008967:Molecular Biology / Q000379:methods*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D009498:Neurotoxins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C036293:prostaglandin D2 receptor