American Association for Cancer Research
00085472can192104-sup-225372_3_supp_6145203_q7dx3d.xlsx (7.1 MB)

Table S1 : RNA-seq data from Lgr5-GFP+ cells from Loss of Apc Rapidly Impairs DNA Methylation Programs and Cell Fate Decisions in Lgr5+ Intestinal Stem Cells

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posted on 2023-03-31, 03:07 authored by Marco Bruschi, Laure Garnier, Elouan Cleroux, Alicia Giordano, Michael Dumas, Anaïs F. Bardet, Thomas Kergrohen, Stanislas Quesada, Pierre Cesses, Michael Weber, François Gerbe, Philippe Jay

This file contains all RNAseq results for gene expression comparisons between FACS sorted ApcWT-, ApcHET-, and ApcKO-Lgr5-GFP profiles.


ITMO Cancer

SIRIC Montpellier Cancer




European Research Council



Colorectal cancer initiation and progression result from the accumulation of genetic and epigenetic alterations. Although aberrant gene expression and DNA methylation profiles are considered hallmarks of colorectal cancer development, the precise timing at which these are produced during tumor establishment remains elusive. Here we investigated the early transcriptional and epigenetic changes induced by adenomatous polyposis coli (Apc) inactivation in intestinal crypts. Hyperactivation of the Wnt pathway via Apc inactivation in crypt base columnar intestinal stem cells (ISC) led to their rapid accumulation driven by an impaired molecular commitment to differentiation, which was associated with discrete alterations in DNA methylation. Importantly, inhibiting the enzymes responsible for de novo DNA methylation restored the responsiveness of Apc-deficient intestinal organoids to stimuli regulating the proliferation-to-differentiation transition in ISC. This work reveals that early DNA methylation changes play critical roles in the establishment of the impaired fate decision program consecutive to Apc loss of function. This study demonstrates the functional impact of changes in DNA methylation to determine the colorectal cancer cell phenotype following loss of Apc function.