Transcriptomic Regulation Driven by TCF12 Isoform Switching

TCF12 is a member of the basic helix–loop–helix (bHLH) transcription factor family, which functions through homo- or heterodimerization with other bHLH proteins to regulate gene expression during development. We identified an alternative splicing event at exon 15 (E15) of TCF12 that differs among glioma cell states, with E15 more frequently included in NPC- and OPC-like states, but less included in MES- and AC-like states. To investigate the biological function of this isoform switch, we employed a dCasRx-RBM25/gRNA system to promote E15 inclusion in a patient-derived glioma stem-like cells (GSC1478) and performed RNA-seq to profile transcriptomic changes. Overall design: RNA-seq profiling of GSC1478 cells treated with dCasRx-RBM25 only, dCasRx-RBM25 with control gRNA, or gRNA-I16 and I19 that induce TCF12 E15 inclusion.