Evidence map›Paper›PMID 39914387›Full record

ArticleCell genomics2025

Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling.

Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
–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

15 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Matthew J RegnerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Susana Garcia-RecioLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Aatish ThennavanDepartment of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Kamila WisniewskaLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Raul Mendez-GiraldezLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Brooke FelsheimLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Philip M SpanheimerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Joel S ParkerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Charles M PerouLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Hector L FrancoLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Clinical and Translational Cancer Research, University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00935, USA. Electronic address: hfranco@cccupr.org.

Funding

Predicting Endocrine Therapy Response In Male Breast TumorsR37CA292075 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jose P. Leone, Philip M. Spanheimer · 2024 to 2026
$1.8M
Predoctoral Training Program in Bioinformatics and Computational BiologyT32GM135123 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael Isaiah Love, William Valdar · 2021 to 2026
$1.7M
Posttranslational Regulation of FOXA1 in Breast CancerR01CA273444 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hector Luis Franco · 2022 to 2026
$1.7M
Repurposing RET Inhibitors for Endocrine Resistant Breast CancerK08CA280388 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Philip M. Spanheimer · 2023 to 2026
$812k
NCI NIH HHS K08 CA280388NCI NIH HHS R01 CA273444NCI NIH HHS R37 CA292075NIGMS NIH HHS T32 GM135123
6 · The paper itself

Abstract

Annotation of cis-regulatory elements that drive transcriptional dysregulation in cancer cells is critical to understanding tumor biology. Herein, we present matched chromatin accessibility (single-cell assay for transposase-accessible chromatin by sequencing [scATAC-seq]) and transcriptome (single-cell RNA sequencing [scRNA-seq]) profiles at single-cell resolution from human breast tumors and healthy mammary tissues processed immediately following surgical resection. We identify the most likely cell of origin for subtype-specific breast tumors and implement linear mixed-effects modeling to quantify associations between regulatory elements and gene expression in malignant versus normal cells. These data unveil cancer-specific regulatory elements and putative silencer-to-enhancer switching events in cells that lead to the upregulation of clinically relevant oncogenes. In addition, we generate matched scATAC-seq and scRNA-seq profiles for breast cancer cell lines, revealing a conserved oncogenic gene expression program between in vitro and in vivo cells. This work highlights the importance of non-coding regulatory mechanisms that underlie oncogenic processes and the ability of single-cell multi-omics to define the regulatory logic of cancer cells.

Indexed as

Breast NeoplasmsEpigenesis, GeneticGene Expression ProfilingSingle-Cell AnalysisCell Line, TumorChromatinFemaleGene Expression Regulation, NeoplasticHumansSequence Analysis, RNATranscriptomeChromatinbreast cancerchromatin accessibilityenhancer elementsgene regulationscATAC-seqscRNA-seqsingle-cell genomicssingle-cell multi-omics

Identifiers

PMID39914387
PMCPMC11872555

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.