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. 2020 Nov 17;27(6):876–889.e12. doi: 10.1016/j.stem.2020.11.009

Figure 5.

Figure 5

Antiandrogenic Drugs Reduce ACE2 and SARS-CoV-2 Infection in hESC-Derived Lung Organoids

(A) Immunofluorescence staining of hESC-derived lung organoids (HLOs) for epithelial lineage markers SOX9, NKX2.1, and ECAD and SARS-CoV-2 receptor ACE2.

(B) Expression analysis of lineage-specific markers during HLO differentiation measured using bulk RNA sequencing at days 0, 5, 9, 15, 25, 35, and 50.

(C) UMAP visualization of single-cell RNA sequencing data showing different epithelial cell clusters in differentiated HLOs.

(D) Dot plot visualization of single-cell expression of epithelial subtype-specific lineage markers in different cell clusters.

(E) Violin plot visualization of single-cell expression of SARS-CoV-2 receptors and androgen signaling genes in different lung epithelial cell clusters.

(F) Effect of antiandrogenic drugs on ACE2 levels in HLOs.

(G and H) Quantification (G) and representative images of immunofluorescence staining (H) of SARS-CoV-2 N-protein in HLOs treated with antiandrogenic drugs prior to infection with SARS-CoV-2 isolate USA/CA-UCSF-0001C/2020.

(I) Plaque assay quantification of viral titers in supernatants of infected HLOs treated with antiandrogenic drugs.

(J and K) Quantification (J) and representative images of immunofluorescence staining (K) of viral double-strand RNA (dsRNA) and SARS-CoV-2 N-protein in infected HLOs treated with dutasteride prior to infection with SARS-CoV-2 isolate USA-WA1/2020, NR-52281.

Scale bar = 100 μm in (A) and 50 μm in (H) and (K). ∗p value < 0.05, ∗∗p value < 0.01, ∗∗∗p value < 0.001. Data are represented as mean ± SEM. See also Figure S5.