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

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