Fig. 3: Potential phenotypic screening approach to identify CSC-specific inhibitors of G9a.
From: Emerging role of G9a in cancer stemness and promises as a therapeutic target
High-content imaging and Microscopic Imaging of Epigenetic Landscape (MIEL) analysis on t-hESCs or patient-derived CSCs identify compounds that induce key phenotypes (e.g., loss of H3K9me2 deposition and/or OCT4 expression). The application of a cancer-selectivity screening step (or filter) involving CSCs vs. their healthy counterparts enables the exclusion of noncancer-specific compounds. In parallel with mechanistic validation experiments, low-to-medium throughput screening for molecular candidates restricting self-renewal and tumor-initiating activity can be performed using patient-derived serial organoid plating assays.
