Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas

Purpose: The purpose of this study was to assess the effect of targeting the Acvr1G328V mutation to oligoendrocyte lineage cells, on gene expression in the brainstem of mice at postnatal day 7 Methods: Total RNA was extracted from the brainstem of postnatal day 7 Acvr1+/+;Olig2Cre/+ and Acvr1floxG328V/+;Olig2Cre/+ littermates, processed using the Illumina TruSeq Stranded Total RNA Sample Preparation kit, and subjected to deep sequencing. Results: A total of 247 genes were differentially expressed between the genotypes, with a corrected p value of less than 0.05. Of these genes, 125 were upregulated while 122 were downregulated. Many of the most downregulated genes were mature oligodendrocyte markers, while several genes that control oligodendrocyte progenitor formation and function were upregulated. Conclusions: The Acvr1G328V mutation causes differentiation arrest of oligodendroglial lineage cells. Brainstem RNA was profiled from postnatal day 7 control (Acvr1+/+;Olig2Cre/+) and mutant (Acvr1floxG328V/+;Olig2Cre/+) littermates, using the Illumina TruSeq Stranded Total RNA Sample Preparation kit and a Nextseq 500 sequencer (Illumina). Samples were processed in two separate batches: The first batch comprised three samples per genotype, and the second batch comprised two samples per genotype. The batch number for each sample is indicated in the sample description.