Supplementary Figure 1: Transgenic assays to track cell behaviour used in this study.

(a) cre-mediated recombination allows for conditional expression of a heritable genetic label. cre recombinase activity is subject to dual regulation, at the transcriptional level and at the level of nuclear translocation. Expression of a cre recombinase-mutant oestrogen receptor fusion protein (cre^ERT) from a drug-regulated promoter is achieved upon treatment with β-napthoflavone (BNF). Upon binding of tamoxifen (Tam), the fusion protein changes conformation and translocates to the nucleus, where it mediates recombination of the loxP sites, thus activating reporter (b,c) or mutant (d) alleles. (b) Genetic lineage tracing in Ahcre^ERTRosa26^{flConfetti/wt} mice. The multicolour confetti reporter allele encodes four fluorescent proteins. Different cre-mediated inversion and excision recombination events result in the heritable expression of one of the four fluorescent proteins depicted, green fluorescent protein (GFP), yellow fluorescent protein (YFP), red fluorescent protein (RFP) or cyan fluorescent protein (CFP). Once recombination is achieved, the reporter will be expressed in all the progeny of the marked cell, which continue to proliferate and differentiate, generating clusters of labelled cells termed clones. (c) Genetic lineage tracing in Ahcre^ERTRosa26^flYFP/wt mice. Induction of cre recombination results in excision of a stop cassette and heritable expression of the single colour yellow fluorescent protein (YFP) reporter. (d) Induction of the oncogenic LSL-Kras^G12D mutant allele. cre-mediated recombination results in the excision of a STOP cassette and heritable expression of the Kras mutant (red star). (e) For quantification of the cell division rate, animals carrying a reverse tetracycline-controlled transactivator (rtTA-M2) and a HIST1H2BJ/EGFP fusion protein (HGFP) expressed from a tetracycline responsive promoter element were used. Doxycycline (dox) treatment in these animals results in nuclear labelling of all basal cells in the oesophageal epithelium with HGFP. Upon withdrawal of dox, HGFP transcription and translation ceases and the protein is diluted by cell division (see Supplementary Note 2.1).