RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence

•Colon tumors contain therapy-resistant quiescent cancer stem cells (qCSCs)•qCSC gene expression mirrors that of the regenerating gut•qCSCs are enriched for p53 signaling genes•qCSC elimination may be achieved by inhibiting downstream targets Recent data suggest (qCSCs) source relapse in colon cancer. Here, using patient-derived organoids and xenografts, we identify rare long-term label-retaining qCSCs can re-enter cell cycle to generate new tumors. RNA sequencing analyses demonstrated these display molecular hallmarks tissue cells, including genes, transcripts common damage-induced revival intestine. In addition, negative regulators cycle, p53, show indicators poor prognosis targeted qCSC abolition both wild-type mutant These support temporal inhibition signaling, combination with standard-of-care treatments, prevention Molecular functional intratumoral heterogeneity contributes differences treatment outcomes between patients similar mutational profiles (Kreso et al., 2013Kreso A. 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Previous studies observed demonstrate stable development. profile carried out PKH26Negative (cycling) (non-cycling) isolated six different S1) cell-associated sets, such embryonic development, organ placenta, nervous epithelial-mesenchymal transition, Wnt, 3A). At time showing genes associated downregulated protein synthesis, metabolism, biosynthesis 3B 3C). agreement transcriptional cycling/qCSCs Me