Extended Data Figure 8: ATOH1-dependent lineage conversion.

a–d, BrdU tracing 1 and 3 days after label injection, showing similar turnover of intestinal epithelial cells in wild-type and Atoh1-null intestines in the absence of Notch inhibition. Nearly all the label is in the villus base at 1 day and in the top halves of villi at 3 days. e, Lineage tracing 3 days after induction of Cre activity by tamoxifen in Lgr5^cre-ER;Rosa26^YFP mice (left) or by RU486 in Atoh1^cre-PR;Rosa26^YFP mice (right). YFP is detected in numerous whole crypts (except Paneth cells) in the former, and never in crypts, ribbons or cell pairs in the latter, confirming absence of leaky Cre^PR expression in multipotent progenitors. f, YFP signal in Atoh1^cre-PR;Rosa26^YFP mice 3 days after RU486-induced Cre activation is confined to scattered ChgA⁺ enteroendocrine and Muc2⁺ goblet cells. g, Two additional representative examples of YFP-traced cell groups that had converted into TFF3-negative enterocytes after Atoh1 deletion in secretory cells. Arrows indicate rare (∼5%, see text) YFP⁺ cells that still express TFF3. Scale bars, 50 μm. Tissues were analysed in duplicate from four (WT, Atoh1^−/−, Atoh^cre-PR/+;Rosa26^YFP) or six (Lgr5^cre-ER;Rosa26^YFP) mice.