Extended Data Fig. 2: Remarkable 3D chromatin reorganization during NE transformation of isogenic PCa cells. | Nature Genetics

Extended Data Fig. 2: Remarkable 3D chromatin reorganization during NE transformation of isogenic PCa cells.

From: NKX2-1 drives neuroendocrine transdifferentiation of prostate cancer via epigenetic and 3D chromatin remodeling

Extended Data Fig. 2

a, Representative brightfield images showing the morphology of FOXA2-OE cells at days 7, 14, 21 and 28. LNCaP cells were infected with control (plv) or FOXA2 virus and followed up for 28 days. Cells were imaged every week. Scale bar: 100 μm. b, FOXA2 OE induced NET in 22Rv1 (left) and DU145 (right) cells. 22Rv1 or DU145 cells were infected with control (plv) or FOXA2 virus, and 22Rv1 cells were collected for WB analysis at week 4, whereas DU145 cells were collected at day 7. The data shown for 22Rv1 are from one of two independent experiments (n = 2), and those for DU145 are from one of three independent experiments (n = 3). c, LNCaP cells were co-infected with sgRB1&TP53 virus along with either sgNC or sgFOXA2 virus for 4 weeks before WB. The data shown are from one of two independent experiments (n = 2). d, Tumor growth curve of control (plv, n = 4 mice) and FOXA2-OE (n = 6 mice) LNCaP xenograft tumors. Data are mean ± s.d., and p value by two-sided t test. e, Hematoxylin and Eosin (H&E) of control (plv) and FOXA2-OE LNCaP xenograft tumors. Representative H&E images (×4) of FOXA2-OE tumors (n = 4) are shown on the left. The circled region indicates the tumor region with small-cell carcinoma-like features, and the high magnification images of small-cell carcinoma and adenocarcinoma tumors (×40) are shown in the middle. Scale bar, 30 µm. The percentage of small-cell carcinoma and adenocarcinoma tumors in the control and FOXA2-OE groups is quantified on the right. f, IHC of FOXA2 and SYP proteins in control (plv) and FOXA2-OE LNCaP xenograft tumors. Representative IHC images of FOXA2+/SYP+ and FOXA2+/SYP− tumors in the FOXA2-OE group (n = 4) are shown on the left, and the quantification of them is shown on the right. Scale bar, 30 µm. Insets are shown at higher magnification. g, Unsupervised hierarchical clustering of time-course LNCaP+FOXA2 samples, CRPC and NEPC (in red font) based on the top 25% most variable PC1 of Hi-C matrices.

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