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Publication
Differential pre-malignant programs and microenvironment chart distinct paths to
malignancy in human colorectal polyps.
Authors Chen B, Scurrah CR, McKinley ET, Simmons AJ, Ramirez-Solano MA, Zhu X, Markham
NO, Heiser CN, Vega PN, Rolong A, Kim H, Sheng Q, Drewes JL, Zhou Y,
Southard-Smith AN, Xu Y, Ro J, Jones AL, Revetta F, Berry LD, Niitsu H, Islam M,
Pelka K, Hofree M, Chen JH, Sarkizova S, Ng K, Giannakis M, Boland GM, Aguirre
AJ, Anderson AC, Rozenblatt-Rosen O, Regev A, Hacohen N, Kawasaki K, Sato T,
Goettel JA, Grady WM, Zheng W, Washington MK, Cai Q, Sears CL, Goldenring JR,
Franklin JL, Su T, Huh WJ, Vandekar S
Submitted By Submitted Externally on 1/10/2022
Status Published
Journal Cell
Year 2021
Date Published 12/1/2021
Volume : Pages 184 : 6262 - 6280.e26
PubMed Reference 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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