Evidence map›Paper›PMID 41384492›Full record

ArticleeLife2025

Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics.

Inbal Avraham-Davidi, Simon Mages, Johanna Klughammer, Noa Moriel, Shinya Imada, Matan Hofree, Evan Murray, Jonathan Chen, Karin Pelka, Arnav Mehta and 17 more

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Article
  2. Article
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  5. Article
  6. Review
  7. MEX3A Modulates PPARγ Pathway Activity and Colorectal Cancer Growth.Cellular and molecular gastroenterology and hepatology · 2026
    Article
  8. Developmental regulation of intestinalbioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Rehydration rescues Il22Nature communications · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
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  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Inbal Avraham-Davidi *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0001-7118-9179
Simon Mages *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0003-1447-6811
Johanna Klughammer *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0002-3628-9278
Noa MorielSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shinya ImadaDepartmen of Biology at MIT, Koch Institute for Integrative Cancer Research at MIT, Cambridge, United States.
Matan HofreeKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.
Evan MurrayBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Jonathan ChenBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Karin PelkaBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Arnav MehtaBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Genevieve M BolandBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Toni DeloreyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0001-6614-3803
Leah CaplanKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0002-6594-1608
Danielle DionneKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.
Robert StrasserGene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Jana Lalakova10xGenomics, Stockholm, Sweden.
Anezka Niesnerova10xGenomics, Stockholm, Sweden.
Hao Xu10xGenomics, Stockholm, Sweden.
Morgane Rouault10xGenomics, Stockholm, Sweden.
Itay TiroshDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.ORCID https://orcid.org/0000-0001-5477-2987
Hacohen NirBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Fei ChenBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States.
Omer YilmazDepartmen of Biology at MIT, Koch Institute for Integrative Cancer Research at MIT, Cambridge, United States.ORCID https://orcid.org/0000-0002-7577-4612
Jatin RoperDepartmen of Biology at MIT, Koch Institute for Integrative Cancer Research at MIT, Cambridge, United States.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.
Mor NitzanSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States.ORCID https://orcid.org/0000-0003-3293-3158

Funding

Tool and Technology Development CoreU19MH114821 · NIMH · COLD SPRING HARBOR LABORATORY · PI MITRA, PARTHA PRATIM · 2017 to 2021
$64.5M
Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Systematic dissection of gut cellular circuits [at single cell resolution]RC2DK114784 · NIDDK · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, GRAHAM, DANIEL BARTHOLOMEW · 2017 to 2021
$9.0M
Trinity: Transcriptome assembly for genetic and functional analysis of cancerU24CA180922 · NCI · BROAD INSTITUTE, INC. · PI HAAS, BRIAN · 2013 to 2022
$7.5M
Effects of inflammaging on intestinal epithelial cells and aspirin chemoprevention.R01CA257523 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAN, ANDREW T, STAPPENBECK, THADDEUS S · 2021 to 2025
$3.7M
Adipose tissue-colorectal tumor cross-talk: new targets for breaking the obesity-cancer linkR01CA254108 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HURSTING, STEPHEN D, ULRICH, CORNELIA M · 2021 to 2025
$3.2M
Targeting plasma membrane spatial dynamics to suppress aberrant Wnt signalingR01CA244359 · NCI · TEXAS A&M AGRILIFE RESEARCH · PI CHAPKIN, ROBERT STEPHEN, KARPAC, JASON S · 2020 to 2024
$2.7M
(PQ3) The role of damaged DNA in inter-individual variation of tumor immunityR01CA208756 · NCI · BROAD INSTITUTE, INC. · PI HACOHEN, NIR · 2016 to 2020
$2.6M
Role of immune regulation in colorectal cancer chemotherapeutic responseR01CA256530 · NCI · YALE UNIVERSITY · PI LU, JUN · 2021 to 2025
$2.4M
Wnt signaling in obesity-associated colorectal cancerR37CA259363 · NCI · DUKE UNIVERSITY · PI Jatin Roper · 2022 to 2026
$1.8M
Malignant Cell Engagement in Immune Circuits of Human Microsatellite-stable and Microsatellite-instable Colorectal CancerR00CA259511 · NCI · J. DAVID GLADSTONE INSTITUTES · PI PELKA, KARIN · 2021 to 2023
$747k
Ultra-bright fluorescent nanoparticles for colorectal adenoma detectionR21DK125911 · NIDDK · DUKE UNIVERSITY · PI ROPER, JATIN, SOKOLOV, IGOR · 2021 to 2022
$461k
Deutsche Forschungsgemeinschaft research fellowship MA 9108/1-1DOD Prostate Cancer Research Program W81XWH-20-1-0203Human Frontier Science Program LT000452/2019-LIsrael Science Foundation 1079/21National Institute of Allergy and Infectious Diseases 1RC2 DK114784National Institute of Allergy and Infectious Diseases 1U19 MH114821National Institute of Allergy and Infectious Diseases 1U24 CA180922NCI NIH HHS NIH/NCI R00CA259511NCI NIH HHS NIH/NCI R01 CA208756NCI NIH HHS NIH/NCI R01CA257523NCI NIH HHS R00 CA259511NCI NIH HHS R01 CA208756NCI NIH HHS R01 CA244359NCI NIH HHS R01 CA254108NCI NIH HHS R01 CA256530NCI NIH HHS R01 CA257523NCI NIH HHS R21 CA256414NCI NIH HHS R37 CA259363NCI NIH HHS U24 CA180922NHGRI NIH HHS 5RM1HG006193-09NHGRI NIH HHS RM1 HG006193NIBIB NIH HHS R41 EB032693NIDDK NIH HHS R21 DK125911NIDDK NIH HHS RC2 DK114784NIH HHS NIH R37CA259363NIH HHS R01CA244359NIH HHS R01CA254108NIH HHS R01CA256530NIH HHS R21CA256414NIH HHS R21DK125911NIH HHS R41EB032693NIMH NIH HHS U19 MH114821SU2C Peggy Prescott Early Career Scientist Award PA-6146SU2C Phillip A. Sharp Award SU2C-AACR-PS-32
6 · The paper itself

Abstract

While advances in single-cell genomics have helped to chart the cellular components of tumor ecosystems, it has been more challenging to characterize their specific spatial organization and functional interactions. Here, we combine single-cell RNA-seq, spatial transcriptomics by Slide-seq, and in situ multiplex RNA analysis to create a detailed spatial map of healthy and dysplastic colon cellular ecosystems and their association with disease progression. We profiled inducible genetic CRC mouse models that recapitulate key features of human CRC, assigned cell types and epithelial expression programs to spatial tissue locations in tumors, and computationally used them to identify the regional features spanning different cells in the same spatial niche. We find that tumors were organized in cellular neighborhoods, each with a distinct composition of cell subtypes, expression programs, and local cellular interactions. Comparing to scRNA-seq and bulk RNA-seq data from human CRC, we find that both cell composition and layout features were conserved between the species, with mouse neighborhoods correlating with malignancy and clinical outcome in human patient tumors, highlighting the relevance of our findings to human disease. Our work offers a comprehensive framework that is applicable across various tissues, tumors, and disease conditions, with tools for the extrapolation of findings from experimental mouse models to human diseases.

Indexed as

Colorectal NeoplasmsSingle-Cell AnalysisTranscriptomeAnimalsDisease Models, AnimalGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMicecancer biologycolorectal cancermousespatial transcriptomicstumor microenvironment

Identifiers

PMID41384492
PMCPMC12700527

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.