Fig. 6: Notch signaling in absorptive versus secretory cell fate decision.

a, KEGG pathway enrichment analysis at different timepoints after the start of dox treatment. b, Notch signaling pathway in ISC differentiation toward absorptive and secretory lineage; two possible mechanisms involving a gradual change or an on/off switch in Notch signaling are shown. c, Cells expressing at least one of following three genes—Atoh1, Spdef and Gfi1 (left) or Notch1, Hes1 and Hes5 (right)—in scRNA-seq are shown in UMAP of Fig. 4g. d,e, Genome browser view of MeD-seq DCM reads (average of n = 3) in Notch1 and its target genes Hes1 and Hes5 and quantification of DCM signal normalized to day 1 (dashed lines represent −dox signal per gene, average plotted with ± s.e.m.). f,g, As in e,f but now for Atoh1, Spdef and Gfi1 (average plotted with ± s.e.m.). Bottom tracks in f show ATOH1 ChIP-seq signal from Atoh1 GFP⁺ cells from the small intestine (ATOH1-targeted regulatory regions are indicated in gray and gene bodies in brown).