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

Autor: Diana Toli, Dorothée Buttigieg, Stéphane Blanchard, Thomas Lemonnier, Boris Lamotte d’Incamps, Sarah Bellouze, Gilbert Baillat, Delphine Bohl, Georg Haase
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Neurobiology of Disease, Vol 82, Iss , Pp 269-280 (2015)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2015.06.011
Popis: 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 p75NTR surface epitope and an HB9::RFP lentivirus reporter. The p75NTR/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.
Databáze: Directory of Open Access Journals
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