Consequential insights for advancing informal STEM learning and outcomes for students from historically marginalized communities.

Consequential STEM experiences in informal settings can address issues of equity by fully engaging historically marginalized high school students in complex socio-scientific issues. However, inclusive and effective programs are in high demand, and there is little research on what specific aspects, context, and timeframes are most important when scaling these experiences. Using a mixed method approach, this study demonstrates that students make significant gains, in the short and long term, through in-person and remote informal programs ranging between 22-h and 320-h. Progress across STEM learning constructs is attributed to authentic research experiences, students' connections to STEM professionals, direct hands-on participation in projects, and group work. Relative to formal education settings, research-based informal STEM programs can be implemented with minimal resources, can maintain effectiveness while scaling, and work towards addressing the societal challenge of improving STEM learning and outcomes for high school students from historically marginalized communities.

Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell-state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing nongenetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupt acquired resistance in GBM.

Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing non-genetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupts acquired resistance in GBM.