Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma [RNA-seq]

Chi3l1 (Chitinase 3-like 1) is a secreted protein highly expressed in glioblastoma. Here, we show that exposure of glioma stem cells (GSCs) to Chi3l1 reduces the CD133+/SOX2+ cells and increases the CD44+/Chi3l1+ cells. Single cell RNA-seq and RNA velocity following incubation of GSCs with Chi3l1 show significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq reveals that Chi3l1 increases accessibility of promoters containing MAZ transcription factor footprint. Inhibition of MAZ directly regulates genes with highest expression in cellular clusters exhibiting significant cell state transitions. Overall design: To identify genes that are potentially directly regulated by MAZ following Chi3l1 treatment, we combined MAZ footprinting prediction from ATAC-seq data with RNA-seq data following MAZ knockdown.