Multiparametric Signature of Glioblastoma Differentiation Revealed by Imaging of Cellular Epigenetic Landscapes

Abstract

The resistance of Glioblastoma (GBM) to conventional cytotoxic drugs has prompted novel therapeutic strategies, including differentiating tumor propagating cells (TPCs) into less tumorigenic cells using small molecule inducers of TPC differentiation. However, high-throughput screening for such molecules is hampered by the lack of robust markers of GBM differentiation. To obtain a signature of differentiated TPCs, we developed \"Microscopic Imaging of Epigenetic Landscapes\" (MIEL), which captures patterns of nuclear staining for epigenetic marks to derive feature-fingerprints of individual cells. We confirmed MIELs ability to accurately distinguish multiple cell fates and identified a multiparametric epigenetic signature of differentiated TPCs. Critically, we validated epigenetic imaging-based signature using global gene expression thus providing the proof of principle for the MIELs ability to select and prioritize small molecules, which induce TPC differentiation.