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© Uwe Maskos
Tranche d'hippocampe de souris colorée avec deux toxines spécifiques de sous-types de récepteur nicotinique, en rouge (grains), et en vert (corps cellulaires). L'hippocampe est la zone du cerveau qui gère la mémoire spatiale.
Publication : Neurobiology of disease

Modeling amyotrophic lateral sclerosis in pure human iPSc-derived motor neurons isolated by a novel FACS double selection technique

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Neurobiology of disease - 21 Jun 2015

Toli D, Buttigieg D, Blanchard S, Lemonnier T, Lamotte d'Incamps B, Bellouze S, Baillat G, Bohl D, Haase G

Link to Pubmed [PMID] – 26107889

Neurobiol. Dis. 2015 Oct;82:269-80

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease. Human motor neurons generated from induced pluripotent stem cells (iPSc) offer new perspectives for disease modeling and drug testing in ALS. In standard iPSc-derived cultures, however, the two major phenotypic alterations of ALS–degeneration of motor neuron cell bodies and axons–are often obscured by cell body clustering, extensive axon criss-crossing and presence of unwanted cell types. Here, we succeeded in isolating 100% pure and standardized human motor neurons by a novel FACS double selection based on a p75(NTR) surface epitope and an HB9::RFP lentivirus reporter. The p75(NTR)/HB9::RFP motor neurons survive and grow well without forming clusters or entangled axons, are electrically excitable, contain ALS-relevant motor neuron subtypes and form functional connections with co-cultured myotubes. Importantly, they undergo rapid and massive cell death and axon degeneration in response to mutant SOD1 astrocytes. These data demonstrate the potential of FACS-isolated human iPSc-derived motor neurons for improved disease modeling and drug testing in ALS and related motor neuron diseases.

http://www.ncbi.nlm.nih.gov/pubmed/26107889