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Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS

Meyer, Kathrin, Ferraiuolo, Laura, Miranda, Carlos J., Likhite, Shibi, McElroy, Sohyun, Renusch, Samantha, Ditsworth, Dara, Lagier-Tourenne, Clotilde +7 more·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1314085111
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Abstract

Significance: Direct conversion is a recently established method to generate neuronal progenitor cells (NPCs) from skin fibroblasts in a fast and efficient manner. In this study, we show that this method can be used to model neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Because the origin of ALS is mainly sporadic with unknown cause, methods to model the disease are urgently needed. The produced NPCs are differentiated into astrocytes, which are involved in motor neuron death in ALS. Strikingly, skin-derived astrocytes show similar toxicity toward motor neurons as astrocytes from autopsies of patients. This tool now allows studying ALS while the patient is still alive and can help in testing potential therapeutics for individual patients.

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Research works printed but not linked: 23

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Authors
Meyer, K., Ferraiuolo, L., Miranda, C. J., Likhite, S., McElroy, S., Renusch, S., Ditsworth, D., Lagier-Tourenne, C., Smith, R. A., Ravits, J., Burghes, A. H., Shaw, P. J., Cleveland, D. W., Kolb, S. J., & Kaspar, B. K.
Affiliations
  • The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205;
  • Department of Neuroscience, The Ohio State University, Columbus, OH 43210;
  • Ludwig Institute for Cancer Research, Department of Medicine and Neuroscience, University of California, San Diego, La Jolla, CA 92093;
  • Center for Neurologic Study, La Jolla, CA 92037;
  • Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093;
  • Department of Molecular and Cellular Biochemistry, The Ohio State University Medical Center, Columbus, OH 43210-1228;
  • Academic Unit of Neurology, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, United Kingdom;
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2013-12-30
Volume
111
Issue
2
Pages
829-832
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1314085111
Cited by
345
References
5
Language
en

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