a UMAP visualizations of scRNA-seq data from Hyper- and ENR-organoids. Left, colors indicate the unsupervised clusters. Right, colors indicate different organoids: ENR-organoids (orange dots) and Hyper-organoids (purple dots). b Expression of cell type-specific markers that identify distinct cell types. EE enteroendocrine, PC Paneth cell, GC goblet cell, EC enterocyte, EP enterocyte progenitor, TA transit amplifying. c Stacked histograms showing the proportions of the included cell types in Hyper-organoids derived from either ENR-organoids (up) or primary crypts (down). Hyper-organoids derived from ENR-organoids had a lineage composition similar to those derived from primary crypts. d Schematic diagram of the genetic lineage tracing strategy used to trace endogenous Lgr5 activation. e Representative images of ENR- and Hyper-organoids (with or without 4-OHT induction) using the lineage tracing system. Scale bars, 100 μm. f FACS analysis of tdTomato+ cells in ENR- and Hyper-organoids (with or without 4-OHT induction) (n = 3 wells). P values were determined using one-way ANOVA. ***P < 0.001. Experiments in e and f were independently repeated at least twice with similar results.