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. 2021 Mar 16;184(8):2167–2182.e22. doi: 10.1016/j.cell.2021.03.026

Figure S5.

Figure S5

Drugs and targets protecting against inflammation-driven dysfunction in human cardiac organoids, related to Figure 4

A) Human cardiac organoids were concurrently treated with 100 ng/ml TNF and inhibitors and then functionally assessed at 24 h. n = 4-6 human cardiac organoids from 1 experiment.

B) Validation in an additional cell line. Human cardiac organoids were concurrently treated with 100 ng/ml TNF and inhibitors and then functionally assessed at 24 h. n = 3-23 human cardiac organoids from 1-2 experiments.

(C-F) Human cardiac organoids were concurrently treated with the cardiac cytokine storm and CDK8-STAT1 S727 inhibitors, and then functionally assessed at 24 h. n = 9-21 human cardiac organoids from 2 experiments.

C) Contraction force.

D) Contraction rate.

E) Time from 50% activation to peak.

F) Time to 50% relaxation.

G) Validation of INCB054329 protection in an additional cell line. Time to 50% relaxation. Human cardiac organoids were concurrently treated with the cardiac cytokine storm and INCB054329, and then functionally assessed at 24 h. n = 4-12 human cardiac organoids from 1-2 experiments.

H) Multiple bromodomain extraterminal protein inhibition prevents cardiac cytokine storm induced diastolic dysfunction, presented as change relative to increased relaxation time. n = 8-43 human cardiac organoids from 2-4 experiment.

I) Validation of results in an additional cell line. Multiple bromodomain extraterminal protein inhibition prevents cardiac cytokine storm induced diastolic dysfunction, presented as change relative to increased relaxation time. n = 14-15 for CTRL and cardiac cytokine storm conditions and 4-6 human cardiac organoids from 1-2 experiments.

J) Assessment of INCB054329 efficacy in conditions with cardiac cytokine storm with the addition of TNF. n = 6-16 human cardiac organoids from 1-2 experiments.

K) BRD4 knockdown prevents cardiac cytokine storm induced diastolic dysfunction, presented as normalized relaxation time. n = 5-8 human cardiac organoids from 1 experiment.

L) Representative force trace of a CTRL human cardiac organoid.

M) Representative force trace of different types of arrhythmias in human cardiac organoids treated with cardiac cytokine storm.

N) Arrhythmic events in human cardiac organoids per experiment. n = 4-7 experiments.

CS – cardiac cytokine storm. Data presented as mean ± SEM. Human pluripotent stem cell-derived cardiac cells- HES3 (A,C-F,H,J,K [with no endothelial cells], L-N) or AA (B,G,I) lines. Endothelial cells- RM3.5 (A,C-F,H,J,L-N) or CC(B,G,I) lines. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001, using a one-way ANOVA with Dunnett’s multiple comparisons test compared to TNF (A,B) CS (C-I), CS + AAV6-shSCR (scramble control) (K) or with Tukey’s multiple comparison test (J) or with Kruskal-Wallis comparisons test to CTRL (N).