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Aberrant oligodendroglial-vascular interactions disrupt the Blood Brain Barrier triggering CNS inflammation

Citation

Niu, Jianqin; Kim, Kicheol; Fancy, Stephen; Baranzini, Sergio (2019), Aberrant oligodendroglial-vascular interactions disrupt the Blood Brain Barrier triggering CNS inflammation, v6, UC San Francisco Dash, Dataset, https://doi.org/10.7272/Q63N21KB

Abstract

Disruption of the blood brain barrier (BBB) is critical to initiation and perpetuation of disease in Multiple Sclerosis (MS). We report here an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent remyelination. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in active MS lesions, representing an inability to properly detach from vessels following perivascular migration. These perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte end feet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates this dysfunctional vascular detachment, and also leads to OPC secretion of Wif1, that interferes with Wnt ligand function on endothelial cell tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that it may be both an impediment to OPC lesion recruitment and also a disease perpetuator via disruption of the BBB.

Methods

We purified total RNA from OPC cultured cell of Olig2cre:APCfloxed knock-out and APCfloxed of mice. RNAseq library was prepared using QuantSeq kit (Lexogen) according to the manufacturer’s instructions and sequenced 50-bp single-end on the HiSeq 4000 (Illumina). 

This data is fastq files of Olig2cre:APCfloxed knock-out and APCfloxed at P4 and P9 time-points.