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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer.
Becker, Winston R; Nevins, Stephanie A; Chen, Derek C; Chiu, Roxanne; Horning, Aaron M; Guha, Tuhin K; Laquindanum, Rozelle; Mills, Meredith; Chaib, Hassan; Ladabaum, Uri; Longacre, Teri; Shen, Jeanne; Esplin, Edward D; Kundaje, Anshul; Ford, James M; Curtis, Christina; Snyder, Michael P; Greenleaf, William J.
Afiliação
  • Becker WR; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Nevins SA; Program in Biophysics, Stanford University, Stanford, CA, USA.
  • Chen DC; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Chiu R; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Horning AM; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Guha TK; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Laquindanum R; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Mills M; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Chaib H; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Ladabaum U; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Longacre T; Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Shen J; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Esplin ED; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Kundaje A; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Ford JM; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Curtis C; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Snyder MP; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Greenleaf WJ; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Nat Genet ; 54(7): 985-995, 2022 07.
Article em En | MEDLINE | ID: mdl-35726067
ABSTRACT
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 pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenoma Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenoma Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article