Searching across hundreds of databases
Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by mutations in the astrocytic filament gene GFAP. While astrocytes are thought to have important roles in controlling myelination, AxD animal models do not recapitulate critical myelination phenotypes and it is therefore not clear how AxD astrocytes contribute to leukodystrophy. Here, we show that AxD patient iPSC-derived astrocytes recapitulate key features of AxD pathology such as GFAP aggregation. Moreover, AxD astrocytes inhibit proliferation of human iPSC-derived oligodendrocyte progenitor cells (OPCs) in co-culture and reduce their myelination potential. CRISPR/Cas9-based correction of GFAP mutations reversed these phenotypes. Transcriptomic analyses of AxD astrocytes and postmortem brains identified CHI3L1 as a key mediator of AxD astrocyte-induced inhibition of OPC activity. Thus, this iPSC-based model of AxD not only recapitulates patient phenotypes not observed in animal models, but also reveals mechanisms underlying disease pathology and provides a platform for assessing therapeutic interventions.
Pubmed ID: 30075130 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets CRTH2
View all literature mentionsThis polyclonal targets Human Chitinase 3-like 1
View all literature mentionsThis polyclonal targets MAP2 antibody - Neuronal Marker
View all literature mentionsThis polyclonal targets NEW Fibroblast-specific Protein 1 (S100A4)
View all literature mentionsThis monoclonal targets CD31
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets BrdU
View all literature mentionsThis monoclonal targets Myelin Basic Protein (MBP), aa 82-87
View all literature mentionsThis monoclonal targets Oligodendrocyte Marker O4
View all literature mentionsThis polyclonal targets Human Olig2
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis monoclonal targets Nkx2.2 transcription factor
View all literature mentionsThis polyclonal targets SOX9
View all literature mentionsThis polyclonal targets αB-Crystallin pAb
View all literature mentionsThis monoclonal targets S100 beta
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets Human PODXL
View all literature mentionsThis monoclonal targets Human PODXL
View all literature mentionsThis monoclonal targets Human Unknown
View all literature mentionsThis polyclonal targets SOX2
View all literature mentionsThis monoclonal targets Oct-3/4
View all literature mentionsThis monoclonal targets Nanog
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name B6.Cg-Rag2tm1.1Cgn/J from IMSR.
View all literature mentionsNational resource for investigators utilizing human post-mortem brain tissue and related biospecimens for their research to understand conditions of the nervous system. Federated network of brain and tissue repositories in the United States that collects, evaluates, stores, and makes available to researchers, brain and other tissues in a way that is consistent with the highest ethical and research standards. The NeuroBioBank ensures protection of the privacy and wishes of donors. Provides information to the public about the need for tissue donation and how to register as a donor.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line GM16825 is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CCD-1079Sk is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line IMR-90 is a Finite cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name B6.Cg-Rag2tm1.1Cgn/J from IMSR.
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
National resource for investigators utilizing human post-mortem brain tissue and related biospecimens for their research to understand conditions of the nervous system. Federated network of brain and tissue repositories in the United States that collects, evaluates, stores, and makes available to researchers, brain and other tissues in a way that is consistent with the highest ethical and research standards. The NeuroBioBank ensures protection of the privacy and wishes of donors. Provides information to the public about the need for tissue donation and how to register as a donor.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
