Spatial multi-omics and single-cell transcriptomics uncover senescence-associated cellular programs during colon adenoma to cancer progression
- 1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Abstract
Colorectal cancer develops through a normal-adenoma-carcinoma sequence, yet only 5-10% of adenomas progress to malignancy, and the cellular programs governing that sequence remain poorly defined. Here we generate a spatial multi-omics atlas of human colon adenomas, combining Visium CytAssist and protein co-detection across 24 nonadvanced and advanced tubular adenomas with single-cell resolution Xenium Prime 5K profiling of 101 patient-matched normal, adenoma, and carcinoma cores from 16 patients. Integrating whole-transcriptome and 31-plex protein data identifies nine spatial clusters and two dysplastic epithelial populations that co-express stemness, proliferation, and senescence programs. These programs occupy a shared, spatially confined epithelial niche that expands from adenoma to carcinoma. Spatial analysis revealed GDF15, a senescence-associated secretory factor, mediated the coupling between senescence and stemness in advanced adenomas, and that GDF15-high epithelium locally excludes CD8+ T cells in adenoma and, more broadly, in carcinoma. These findings position senescence as a spatially instructive rather than merely tumor-suppressive program during colorectal carcinogenesis and suggest GDF15 might be a potential candidate target for cancer prevention and interception in the colon.
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BibTeX
@misc{yu2026spatial,
title = {{Spatial multi-omics and single-cell transcriptomics uncover senescence-associated cellular programs during colon adenoma to cancer progression}},
author = {M. Yu and Y. Xie and L. Allen and K. Carter and E. Donato and L. Cheng and C. Kendziorski and K. A. Matkowskyj and A. M. De Marzo and J. Hicks and D. Reddi and E. W. Newell and W. Sun and W. M. Grady},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.06.743310},
url = {https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Spatial multi-omics and single-cell transcriptomics uncover senescence-associated cellular programs during colon adenoma to cancer progression
AU - M. Yu
AU - Y. Xie
AU - L. Allen
AU - K. Carter
AU - E. Donato
AU - L. Cheng
AU - C. Kendziorski
AU - K. A. Matkowskyj
AU - A. M. De Marzo
AU - J. Hicks
AU - D. Reddi
AU - E. W. Newell
AU - W. Sun
AU - W. M. Grady
PY - 2026
DA - 2026/08/06
PB - bioRxiv
DO - 10.64898/2026.08.06.743310
UR - https://www.biorxiv.org/content/10.64898/2026.08.06.743310v2
AB - Colorectal cancer develops through a normal-adenoma-carcinoma sequence, yet only 5-10% of adenomas progress to malignancy, and the cellular programs governing that sequence remain poorly defined. Here we generate a spatial multi-omics atlas of human colon adenomas, combining Visium CytAssist and protein co-detection across 24 nonadvanced and advanced tubular adenomas with single-cell resolution Xenium Prime 5K profiling of 101 patient-matched normal, adenoma, and carcinoma cores from 16 patients. Integrating whole-transcriptome and 31-plex protein data identifies nine spatial clusters and two dysplastic epithelial populations that co-express stemness, proliferation, and senescence programs. These programs occupy a shared, spatially confined epithelial niche that expands from adenoma to carcinoma. Spatial analysis revealed GDF15, a senescence-associated secretory factor, mediated the coupling between senescence and stemness in advanced adenomas, and that GDF15-high epithelium locally excludes CD8+ T cells in adenoma and, more broadly, in carcinoma. These findings position senescence as a spatially instructive rather than merely tumor-suppressive program during colorectal carcinogenesis and suggest GDF15 might be a potential candidate target for cancer prevention and interception in the colon.
ER -