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

• DOI: 10.1073/pnas.1314085111
• Publication Date: 2013-12-31T02:43:06Z
• Authors: Kathrin Meyer; Laura Ferraiuolo; Carlos J. Miranda; Shibi Likhite; Sohyun McElroy; Samantha Renusch; Dara Ditsworth; Clotilde Lagier-T...; Richard A. Smith; John Ravits; Arthur H. Burghes; Pamela J. Shaw; Don W. Cleveland; Stephen J. Kolb; Brian K. Kaspar
• Keywords: Cell Culture Techniques; Stem Cell Research - Embryonic - Non-Human; Fluorescent Antibody Technique; Cell Communication; Neurodegenerative; Real-Time Polymerase Chain Reaction; Models, Biological; 03 medical and health sciences; Rare Diseases; Neural Stem Cells; Clinical Research; Stem Cell Research - Nonembryonic - Human; Models; neurotoxicity; Humans; DNA Primers; Motor Neurons; Analysis of Variance; 0303 health sciences; Biomedical and Clinical Sciences; Stem Cell Research - Induced Pluripotent Stem Cell - Human; Stem Cell Research - Induced Pluripotent Stem Cell; Amyotrophic Lateral Sclerosis; Neurosciences; neurodegeneration; reprogramming; Cell Differentiation; Cell Dedifferentiation; Fibroblasts; Stem Cell Research; Biological; Brain Disorders; 3. Good health; Astrocytes; Neurological; ALS

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