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

2013; National Academy of Sciences; Volume: 111; Issue: 2 Linguagem: Inglês

10.1073/pnas.1314085111

1091-6490

Kathrin Meyer, Laura Ferraiuolo, Carlos J. Miranda, Shibi Likhite, Sohyun L. McElroy, Samantha Renusch, Dara Ditsworth, Clotilde Lagier‐Tourenne, Richard Smith, John Ravits, Arthur H.M. Burghes, Pamela J. Shaw, Don W. Cleveland, Stephen J. Kolb, Brian K. Kaspar,

Neurogenetic and Muscular Disorders Research

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.