Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps
Name
1-s2.0-S0092867421013817-main.pdf
Description
Published version
Size
19.87 MB
Format
Adobe PDF
Checksum (MD5)
1dcd37a291b72304911d0c4109069910
Author(s)
Regev, Aviv
Date Issued
2021
Journal
Cell
Publisher
Elsevier BV
Citation
Regev, Aviv. 2021. "Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps." Cell, 184 (26).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2021.11.031
