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. Author manuscript; available in PMC: 2019 Oct 24.
Published in final edited form as: Nature. 2019 Apr 24;569(7754):66–72. doi: 10.1038/s41586-019-1146-y

Extended Data Figure 10. Yap1 cell-to-cell variability allow a Notch/Dll1 event and symmetry breaking.

Extended Data Figure 10

a, Images showing Yap1 variability and Dll1+ cells. Zoom in: nuclear localization of Hes1 in the same organoid. Arrows: Red (Dll1+ cells), yellow (Hes1+). Scale bar=10 μm. b, Images showing overlap of Paneth cells with Dll1+ cells. c, MIP images (top row) and zoom-in single plane images (bottom row) of: control, Verteporfin added at 48h, Wnt removal at 48h, LATS DKO and Ereg treatment. Organoids are fixed at 72h. d, MIP images (top-row) and zoom-in single plane images (bottom-row) of: control, Verteporfin added at 48h, Wnt removal at 48h, Yap1 overexpression, LATS DKO and Ereg treatment. Organoids are fixed at 72h. e, Fraction of enterocysts (left panel) and fraction of organoids with Paneth cells (right panel) for control and organoids treated with Ly411575 or MK-0752 at 0h. Fixation at 120h. (normalization: control, n=4 replicates, two-sided t-test, p-value Ly411575 0.009, MK-0752 0.003). Barplots: mean ± s.d. f, MIP images (top-row) and zoom-in single plane images (bottom-row) of organoids treated with control or DAPT at 120h and fixed at 144h and stained for AldoB (left panel) or Lys1 (right panel) g, Top panel: annotation enrichment of genes correlated with Yap1 target genes expression in cells expressing Yap1 target genes and Dll1, Dll4, Jag1, Jag2, Atoh1 genes. Bottom panel: annotation enrichment of genes anti-correlated with Yap1 target genes expression in cells expressing Yap1 target genes and Dll1, Dll4, Jag1, Jag2, Atoh1 genes. Enrichment Score (E.S.). h, MIP images of organoids at 120h, showing canonical Wnt signalling response (TCF-GFP) in cells neighbouring Paneth cells.