Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states.

Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional 'tissue-states' defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment.

Injectable Self-Assembling Peptide Hydrogels for Tissue Writing and Embryonic Stem Cell Culture.

The fabrication of extracellular matrix-mimic hydrogels that can nurture and direct differentiation of embryonic stem cells is an important target for pattern-printed tissue replacement. Another desirable feature for such materials is their ability to be injected and recover their rheological features post-injection, allowing for facile non-invasive implantation. In this report, we demonstrate the ability of a self-assembling peptide hydrogel to support the culture of embryonic stem cells with the potential to direct differentiation. We also show that we can write a functional tissue replacement with a predetermined pattern using our formulation. Our results may lead to in vivo replacement of diseased tissue with a spatially resolved pattern of a regenerative hydrogel.