Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of…

• WU
  Washington University in St. Louis
• NI
  National Institutes of Health

  Awards: R01- HG00990901, AI057266, U19-AI057266, UM1-HG009442, RM1-HG007735, HG007735, U19- AI057266, R01-HG00990901, UM1-HG009436, P30DK116074, S10OD025212, T32GM007365
• NH
  National Human Genome Research Institute

  Awards: HG007735, UM1-HG009436, RM1-HG007735
• NC
  National Cancer Institute

  Award: U2C CA233311
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Award: P30DK116074