作者
Bob Chen, Scurrah Cherie’R, Eliot T McKinley, Alan J Simmons, Marisol A Ramirez-Solano, Xiangzhu Zhu, Nicholas O Markham, Cody N Heiser, Paige N Vega, Andrea Rolong, Hyeyon Kim, Quanhu Sheng, Julia L Drewes, Yuan Zhou, Austin N Southard-Smith, Yanwen Xu, James Ro, Angela L Jones, Frank Revetta, Lynne D Berry, Hiroaki Niitsu, Mirazul Islam, Karin Pelka, Matan Hofree, Jonathan H Chen, Siranush Sarkizova, Kimmie Ng, Marios Giannakis, Genevieve M Boland, Andrew J Aguirre, Ana C Anderson, Orit Rozenblatt-Rosen, Aviv Regev, Nir Hacohen, Kenta Kawasaki, Toshiro Sato, Jeremy A Goettel, William M Grady, Wei Zheng, M Kay Washington, Qiuyin Cai, Cynthia L Sears, James R Goldenring, Jeffrey L Franklin, Timothy Su, Won Jae Huh, Simon Vandekar, Joseph T Roland, Qi Liu, Robert J Coffey, Martha J Shrubsole, Ken S Lau
发表日期
2021/12/22
期刊
Cell
卷号
184
期号
26
页码范围
6262-6280. e26
出版商
Elsevier
简介
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 …
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B Chen, S Cherie'R, ET McKinley, AJ Simmons… - Cell, 2021