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Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps.
Chen, Bob; Scurrah, Cherie' R; McKinley, Eliot T; Simmons, Alan J; Ramirez-Solano, Marisol A; Zhu, Xiangzhu; Markham, Nicholas O; Heiser, Cody N; Vega, Paige N; Rolong, Andrea; Kim, Hyeyon; Sheng, Quanhu; Drewes, Julia L; Zhou, Yuan; Southard-Smith, Austin N; Xu, Yanwen; Ro, James; Jones, Angela L; Revetta, Frank; Berry, Lynne D; Niitsu, Hiroaki; Islam, Mirazul; Pelka, Karin; Hofree, Matan; Chen, Jonathan H; Sarkizova, Siranush; Ng, Kimmie; Giannakis, Marios; Boland, Genevieve M; Aguirre, Andrew J; Anderson, Ana C; Rozenblatt-Rosen, Orit; Regev, Aviv; Hacohen, Nir; Kawasaki, Kenta; Sato, Toshiro; Goettel, Jeremy A; Grady, William M; Zheng, Wei; Washington, M Kay; Cai, Qiuyin; Sears, Cynthia L; Goldenring, James R; Franklin, Jeffrey L; Su, Timothy; Huh, Won Jae; Vandekar, Simon; Roland, Joseph T; Liu, Qi; Coffey, Robert J.
Affiliation
  • Chen B; Program in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Scurrah CR; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • McKinley ET; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Simmons AJ; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Ramirez-Solano MA; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Zhu X; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Markham NO; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville
  • Heiser CN; Program in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Vega PN; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Rolong A; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Kim H; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Sheng Q; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Drewes JL; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhou Y; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Southard-Smith AN; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Xu Y; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Ro J; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Jones AL; Vanderbilt Technologies for Advanced Genomics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Revetta F; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Berry LD; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Niitsu H; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Islam M; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Pelka K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
  • Hofree M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen JH; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
  • Sarkizova S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
  • Ng K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Giannakis M; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Boland GM; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
  • Aguirre AJ; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Anderson AC; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Regev A; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Hacohen N; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Kawasaki K; Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Sato T; Department of Organoid Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Goettel JA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Grady WM; Clinical Research Division, Fred Hutchinson Cancer Research Center, and Gastroenterology Division, University of Washington School of Medicine, Seattle, WA, USA.
  • Zheng W; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Washington MK; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cai Q; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Sears CL; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Goldenring JR; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Franklin JL; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Medicine, Division of Gastroenterology,
  • Su T; Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Huh WJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Vandekar S; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Roland JT; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Liu Q; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Coffey RJ; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: robe
Cell ; 184(26): 6262-6280.e26, 2021 12 22.
Article in En | MEDLINE | ID: mdl-34910928
ABSTRACT
Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Colonic Polyps / Tumor Microenvironment Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Colonic Polyps / Tumor Microenvironment Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States