On Thursday (16.10) we will host dr. Katarzyna Leszczyńska (Laboratory of Tumour of Hypoxia and Epigenomics, Nencki Institute of Experimental Biology, PAS). Her lecture will be entitled: " Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs". The lecture will take place at 3 p.m. in the CN lecture hall and it will be followed by a get together.

Abstract

Hypoxia is a key histopathological feature of glioblastoma, associated with tumour aggressiveness and therapy resistance. Glioma-associated microglia and macrophages (GAMs) are key players in the tumour microenvironment of glioblastoma and acquire immunosuppressive properties during tumour progression. We show that hypoxia alters key GAM identity genes, as it upregulates the expression of monocytic marker Lgals3 and downregulates the homeostatic microglial markers P2ry12 and Tmem119 in GAMs co-cultured with glioma cells and in glioblastoma patients’ samples. We further identify hypoxia-dependent dysregulation of numerous GAM subtype and functional markers, which is associated with chromatin accessibility changes, as determined using ATAC-seq. Hypoxia upregulates lipid storage-related genes and accumulation of lipid droplets, which can be reversed upon restoration of H3K27ac with a histone deacetylase inhibitor. We emphasise the importance of hypoxic stress as a strong intratumoral and epigenomic regulator of myeloid cell functions, which adds a new dimension to the characterisation of particular GAM subpopulations.