Transcriptomics,Genomics

Dataset Information

104

Human optic chiasm from healthy controls and multiple sclerosis patients


ABSTRACT: Changes in gene expression that occur across the entire central nervous system (CNS) during disease do not take into account variability from one CNS region to another and can be confounded by alterations in cellular composition during disease. Multiple sclerosis (MS) is characterized by cell proliferation, migration and damage in various cell types in different CNS regions and causes disabilities related to distinct neurological pathways, such as walking, vision and cognition. Here, a cell-specific and region-specific transcriptomic approach was used to determine changes in gene expression in astrocytes derived from spinal cord, cerebellum, cerebral cortex, and hippocampus in the preclinical MS model, chronic experimental autoimmune encephalomyelitis (EAE). RNA sequencing and bioinformatics analysis showed that changes in gene expression pathways in astrocytes differed between neuroanatomic regions. Further, while astrocytes from spinal cord showed increased expression of immune pathway genes during EAE, cholesterol biosynthesis pathway genes were decreased. Translating these findings from the preclinical model to humans, optic nerve from EAE and optic chiasm from MS each showed a significant decrease in cholesterol biosynthesis pathways. Finally, a treatment targeting cholesterol homeostasis in astrocytes was protective in EAE, suggesting a novel neuroprotective strategy for MS. Using a cell-specific and region-specific gene expression approach can provide therapeutically relevant insights into mechanisms underlying specific disabilities in complex multifocal neurological diseases. Overall design: Five MS patients (average age = 56.2 years) and five age-matched healthy controls (average age = 57.6 years) fresh frozen autopsy optic chiasm tissue samples were obtained from Human Brain and Spinal Fluid Research Center in Los Angeles.

INSTRUMENT(S): Illumina HiSeq 3000 (Homo sapiens)

SUBMITTER: Yuichiro Itoh  

PROVIDER: GSE100297 | GEO | 2017-12-23

SECONDARY ACCESSION(S): PRJNA391285

REPOSITORIES: GEO

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Publications

Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Itoh Noriko N   Itoh Yuichiro Y   Tassoni Alessia A   Ren Emily E   Kaito Max M   Ohno Ai A   Ao Yan Y   Farkhondeh Vista V   Johnsonbaugh Hadley H   Burda Josh J   Sofroniew Michael V MV   Voskuhl Rhonda R RR  

Proceedings of the National Academy of Sciences of the United States of America 20171226 2


Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune en  ...[more]

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