Extended Data Fig. 8: Glutamatergic and GABA-ergic signaling drives proliferation of multiple SCLC subtypes via neurotransmitter-mediated signaling pathways.

a, Quantification of proliferative index of human SCLC-A subtype H69 cells co-cultured with human iPSC-derived glutamatergic neurons with or without addition of 50 µM MK801 (inhibitor of NMDA receptor for glutamate) reveals increased proliferation in co-culture abrogated by MK801 (n = 3 coverslips per condition, p = 0.0002). b, As in a, but 50 µM CNQX (inhibitor of AMPA receptor for glutamate) was used (n = 3 coverslips per condition, p = 0.0017). c, As in a, but human SCLC-N subtype H446 cells were used (n = 3 coverslips per condition, p = 0.0005). d, As in a, but human SCLC-P subtype H1048 cells were used (n = 3 coverslips per condition, p = 0.0001). e, Quantification of proliferative index of human SCLC-N subtype H446 cells co-cultured with human iPSC-derived GABA-ergic neurons with or without addition of 1 µM TTX or 20 µM Gabazine (GABA-A receptor inhibitor) reveals increased proliferation in co-culture abrogated by TTX and Gabazine (n = 4–6 coverslips per condition, p < 0.0001). f, As in e, but human SCLC-P subtype H1048 cells were used (n = 3–5 coverslips per condition, p < 0.0001). Data are mean ± s.e.m. Analysis with 2-way ANOVA. ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05.