期刊
NEUROBIOLOGY OF DISEASE
卷 82, 期 -, 页码 269-280出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2015.06.011
关键词
Motor neuron disease; Amyotrophic lateral sclerosis (ALS); Induced pluripotent stem cells (iPSc); Cell death; Axon degeneration; Fluorescent-activated cell sorting (FACS); p75NTR; HB9; Superoxide dismutase 1 (SOD1)
资金
- Agence Nationale pour la Recherche [ANR-08-NEUR-005-02]
- CNRS
- Aix-Marseille University
- Federation pour la Recherche sur le Cerveau
- Association Francaise contre les Myopathies (AFM)
- INSERM
- Institut Pasteur
- Agence Nationale de la Recherche (Laboratoire d'Excellence Revive, Investissement d'Avenir) [ANR-10-LABX-73]
- Association Francaise contre les Myopathies
- Association pour la Recherche sur la Sclerose Laterale Amyotrophique et autres Maladies du Motoneurone (ARS )
- Thierry Latran foundation
- A.S. Onassis Foundation Scholarship
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. (C) 2015 Elsevier Inc. All rights reserved.
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