Evidence map›Paper›PMID 35726067›Full record

ArticleNature genetics2022

Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer.

Winston R Becker, Stephanie A Nevins, Derek C Chen, Roxanne Chiu, Aaron M Horning, Tuhin K Guha, Rozelle Laquindanum, Meredith Mills, Hassan Chaib, Uri Ladabaum and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
194citing papers in PubMed, 1 pooled it
27.1field-weighted citation impact, top 1% of its field
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

194 citing papers in PubMed, 1 synthesis or guideline pooled it, 304 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Epigenetics · 2026
    Article
  4. Review
  5. Article
  6. Single-cell epigenomics of colorectal cancer.Experimental & molecular medicine · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Single-cell transcriptomic analysis reveals cellular heterogeneity and prognostic subtypes in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

134 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Winston R Becker *Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7876-5060
Stephanie A Nevins *Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Derek C ChenDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9652-4885
Roxanne ChiuDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Aaron M HorningDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3247-0798
Tuhin K GuhaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Rozelle LaquindanumDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Meredith MillsDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Hassan ChaibDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Uri LadabaumDivision of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
Teri LongacreDepartment of Pathology, Stanford University, Stanford, CA, USA.
Jeanne ShenDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1519-0308
Edward D EsplinDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9205-3756
Anshul KundajeDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3084-2287
James M FordDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Christina CurtisDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Michael P SnyderDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA. mpsnyder@stanford.edu.ORCID http://orcid.org/0000-0003-0784-7987
William J GreenleafDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA. wjg@stanford.edu.ORCID http://orcid.org/0000-0003-1409-3095
Stanford University · USChan Zuckerberg Initiative (United States) · USStanford Medicine · US

Funding

VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
INSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2M
PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOMEUM1HG009442 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2017 to 2021
$20.1M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
PreCancer Atlas of Familial Adenomatous PolyposisU2CCA233311 · NCI · STANFORD UNIVERSITY · PI FORD, JAMES M., SNYDER, MICHAEL P. · 2018 to 2023
$11.6M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Stanford Tissue Mapping CenterU54HG010426 · NHGRI · STANFORD UNIVERSITY · PI NOLAN, GARRY P, SNYDER, MICHAEL P. · 2018 to 2021
$5.1M
Ultra high throughput sequencer for sustaining and enhancing multi-scale genomic studiesS10OD025212 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2018
$600k
NCI NIH HHS P30 CA124435NCI NIH HHS U2C CA233311NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS T32 HG000044NHGRI NIH HHS U54 HG010426NHGRI NIH HHS UM1 HG009436NHGRI NIH HHS UM1 HG009442NIAID NIH HHS U19 AI057266NIDDK NIH HHS P30 DK116074NIGMS NIH HHS T32 GM007365NIH HHS S10 OD025212
6 · The paper itself

Abstract

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.

Indexed as

AdenomaColorectal NeoplasmsCell Transformation, NeoplasticDNA MethylationHumansSingle-Cell Analysis

Identifiers

PMID35726067
PMCPMC9279149
OpenAlexW4283157828

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.