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. 2024 Oct 16;10(42):eadi6927. doi: 10.1126/sciadv.adi6927

Fig. 3. MYH7-variant hiPSC-CMs drive fibrotic activation of stromal cells via paracrine signaling of EGF.

Fig. 3.

(A) Schematic of conditioned media experiments. (B) Average fold change of EdU+ vCFs after incubation with EdU from hours 20 to 24 of culture in hiPSC-CM conditioned media normalized to WT: WT (n = 10), R403Q+/− (n = 10) (N = 5). (C) Top pathways up-regulated in vCFs given R403Q+/− hiPSC-CM conditioned media compared to WT hiPSC-CM conditioned media, determined from genes (average fold change >1.15 and P value <0.01 from N = 3) input into the WikiPathway database. EV, extracellular vesicle; RLR, RIG-I-like receptor. (D) Transcription factors associated with genes up-regulated in vCFs given R403Q+/− hiPSC-CM conditioned media compared to WT hiPSC-CM conditioned media (average fold change >1.15 and P value <0.01 from N = 3) input into the ChEA 2022 database. (E) Log2 of the fold change of the top 15 cytokines differentially secreted in R403Q+/− compared to WT hiPSC-CM conditioned media. (F) Average percentage of EdU+ vCFs after incubation with EdU from hours 20 to 24 of culture in 100 ng/ml of 10 different human recombinant proteins (n > 5) (N > 2). (G) Top 10 pathways up-regulated in vCFs given rhEGF (100 ng/ml) compared to serum starvation, determined from genes (fold change >1.3 and P value <0.01) input into the WikiPathway database. (H) Change in proliferation rate of serum-starved vCFs given WT or R403Q+/− hiPSC-CM conditioned media with 1 μM erlotinib hydrochloride (EGFRKi) compared to 0.01% DMSO for 24 hours: All conditions (n = 9) (N = 3). Individual sample wells (n) across all independent experiments (N) are shown with means ± SEM unless otherwise noted.