Single-Cell Heterogeneity of EGFR Pathway Is Linked to Unique Signatures of Drug Response and Malignancy in Patient Derived Glioblastoma Stem Cells.

Purpose: In glioblastoma, the therapeutically intractable and resistant phenotypes can be derived from glioma stem cells, which often have different underlying mechanisms from non-stem glioma cells. Aberrant signaling across the EGFR-PTEN-AKT-mTOR pathways have been shown as common drivers of glioblastoma. Revealing the inter and intra-cellular heterogeneity within glioma stem cell populations in relations to signaling patterns through these pathways may be key to precision diagnostic and therapeutic targeting of these cells.

Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity.

Give me a sign(ature): Converging on the CSC of glioblastoma.

The identification of stem cells in glioblastomas has been controversial. In this issue of Neuron, Xie et al. establish gene signatures for cellular states and a quiescent cancer stem cell (qCSC) and demonstrate that the qCSC population expands in recurrence.

Valproic acid targets IDH1 mutants through alteration of lipid metabolism.

Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility.

Acute rapamycin treatment reveals novel mechanisms of behavioral, physiological, and functional dysfunction in a maternal inflammation mouse model of autism and sensory over-responsivity.

Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and neuro-inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that might be expected to alter or prevent physical brain changes.