Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation

Francesco Paolo Di Giorgio; Gabriella L Boulting; Samuel Bobrowicz; Kevin C Eggan

doi:10.1016/j.stem.2008.09.017

Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation

Cell Stem Cell. 2008 Dec 4;3(6):637-48. doi: 10.1016/j.stem.2008.09.017.

Authors

Francesco Paolo Di Giorgio¹, Gabriella L Boulting, Samuel Bobrowicz, Kevin C Eggan

Affiliation

¹ The Harvard Stem Cell Institute, The Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Cambridge, MA 02138, USA.

PMID: 19041780
DOI: 10.1016/j.stem.2008.09.017

Abstract

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.

MeSH terms

Amyotrophic Lateral Sclerosis / genetics
Amyotrophic Lateral Sclerosis / metabolism*
Amyotrophic Lateral Sclerosis / physiopathology
Animals
Animals, Newborn
Cell Communication / genetics
Cell Culture Techniques / methods
Cell Differentiation / genetics
Cell Line
Cell Survival / genetics
Cells, Cultured
Coculture Techniques
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism*
Humans
Mice
Mice, Transgenic
Models, Biological
Molecular Biology / methods*
Motor Neurons / cytology
Motor Neurons / metabolism*
Mutation / genetics
Nerve Degeneration / genetics
Nerve Degeneration / metabolism*
Nerve Degeneration / physiopathology
Neuroglia / metabolism*
Neurotoxins / metabolism
Receptors, Immunologic / genetics
Receptors, Prostaglandin / genetics
Superoxide Dismutase / genetics
Superoxide Dismutase-1

Substances

Neurotoxins
Receptors, Immunologic
Receptors, Prostaglandin
SOD1 protein, human
Sod1 protein, mouse
Superoxide Dismutase
Superoxide Dismutase-1
prostaglandin D2 receptor

Associated data

GEO/GSE13643