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Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis.

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Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

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The authors' code

Shell · 12 lines · 385 B · no license

  1. GENOME_CELLRANGER="~/reference/genome/hg38/10x/refdata-gex-GRCh38-2020-A"
  2. ID="S1"
  3. fq="S1"
  4. SAMPLE="S1"
  5. cellranger count --id "$ID"_cellranger710 \
  6. --transcriptome=$GENOME_CELLRANGER \
  7. --fastqs=$fq \
  8. --localcores=32 \
  9. --localmem=512 \
  10. --sample=$SAMPLE \
  11. --nosecondary

00.10X_Code.sh at commit 69f6903, no license · at the source

Overview

Authors: Haoyuan Shi1, Jiaxin Chen2, Zisheng Wu3,4, Dong-Xu Liu5, Jinmei Zhou4, Xuexue Wu4, Ailing Yang4, Shanhu Li2, Yanhong Tai6, Zefei Jiang4, Zhiyuan Hu7,8,9,10,11, Mingshan Zhang12, Xiaojie Xu2, Lu Pan2, Tao Wang4,13,14
ORCID iDs: Haoyuan Shi, Dong-Xu Liu, Zhiyuan Hu, Mingshan Zhang, Xiaojie Xu, Lu Pan, Tao Wang
14 affiliations
  1. Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing, China
  2. National Key Laboratory of Advanced Biotechnology, Academy of Military Medical Sciences,Beijing, China
  3. Medical School of Chinese PLA,Beijing, China
  4. Senior Department of Oncology, Chinese PLA General Hospital,Beijing, China
  5. Department of Breast Surgery; Shandong Key Laboratory of Cancer Digital Medicine; Institute of Translational Medicine of Breast Disease Prevention and Treatment; and Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, The Second Hospital of Shandong University,Jinan, China
  6. Pathology Department, The Fifth Medical Center of PLA General Hospital,Beijing, China
  7. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology,Beijing, China
  8. School of Future Medicine, Beijing University of Chinese Medicine,Beijing, China
  9. School of Nanoscience and Technology, Sino-Danish College, University of Chinese Academy of Sciences,Beijing, China
  10. Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University,Fuzhou, China
  11. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology,Wuhan, China
  12. Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University,Beijing, China
  13. The Second of Clinical Medicine, Southern Medical University,Guangzhou, China
  14. Anhui Medical University,Hefei, China
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College (China); Academy of Military Medical Sciences (China); Chinese People's Liberation Army (China); Chinese PLA General Hospital (China); Second Hospital of Shandong University (China); National Center for Nanoscience and Technology (China); Beijing University of Chinese Medicine (China); University of Chinese Academy of Sciences (China); Fujian Medical University (China); Wuhan Institute of Technology (China); Capital Medical University (China); Southern Medical University (China); Anhui Medical University (China)
Journal: Cell death & disease, volume 17, issue 1, article 553
Dates: received 24 October 2025; accepted 18 April 2026; published online 25 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41419-026-08807-w · PMID 42034645 · PMCID PMC13247122 · OpenAlex W7155606386
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Breast cancer, Tumour immunology, Biomarkers
MeSH: Brain Neoplasms*, Breast Neoplasms*, Tumor-Associated Macrophages*, Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Metastasis, Neoplastic Cells, Circulating, Single-Cell Gene Expression Analysis, Tumor Microenvironment (* major topic)
Topic: Brain Metastases and Treatment (Pulmonary and Respiratory Medicine, Medicine), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (No. 7232161, 82272762); Beijing Natural Science Foundation (No. Z240016); Capital’s Funds for Health Improvement and research (No. 2024-2-5064), Beijing Science and Technology Medical Development Fund (No. KC2022-ZZ-0091-7), National Key Research and Development Program (No.2023YFA0914900); Postdoctoral Fellowship Program of CPSF (No. GZC20240147)
Citations: not cited yet (Europe PMC); 79 references in the paper

Abstract

Breast cancer brain metastasis (BCBM) is a major cause of breast cancer-related mortality, but the molecular mechanisms underlying its progression remain poorly understood. Here, we profiled the tumor immune microenvironment of BCBM at single-cell resolution and identified candidate regulators associated with brain metastatic progression. Single-cell RNA sequencing (scRNA-seq) was performed on brain metastatic tissue, adjacent tumor tissue, cerebrospinal fluid, and circulating tumor cells (CTCs) from seven patients, and bulk DNA sequencing was conducted on primary breast tumors, peripheral blood, and brain metastases from 47 patients. Analysis of 131,880 single cells identified 63 distinct cell clusters, including 12 tumor-associated macrophage (TAM) subtypes and 5 metastatic tumor cell (MTC) subtypes. Circulating TAMs displayed an M1-like inflammatory phenotype, whereas tissue-resident TAMs were predominantly M2-like. MTCs exhibited substantial transcriptional heterogeneity, and a neuro-related subtype showed adaptive upregulation of neuronal signaling pathways. Brain metastases also harbored a higher mutational burden than primary tumors, with recurrent mutations in GABRB3 and NRXN1 associated with poorer patient survival. Functional experiments further showed that loss of GABRB3 or NRXN1 impaired tumor growth and brain colonization in xenograft models. These findings nominate GABRB3 and NRXN1 as candidate regulators of brain metastatic fitness in BCBM and support their further evaluation as biomarkers and therapeutic targets.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

yuansh3354/scBRCA_BM

License: none: the authors keep all their rights
State: the link answers, verified on 30 September 2026
Evidence: files inventoried
Commit: 69f69034822b687eeadb5eccb36e7cdc34ba7d6d, 10 March 2025
Languages: Shell (5), R (1)
Size: 9 files, 6 scripts
Software Heritage: not archived
Found in: “Data availability”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Cell Ranger (1 file)
Availability: 1 check, the latest on 30 September 2026: the link answers
  • 30 September 2026: the link answers
7 files
At the source: github.com/yuansh3354/scBRCA_BM

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 6 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

All datasets, data processing codes, and configuration files are available on GitHub (https://github.com/yuansh3354/scBRCA_BM). The scRNA-seq data generated in this study are accessible via the China National Center for Bioinformation (BioProject ID: PRJCA020509, Accession Number: HRA008291). High-resolution images and clinical data have also been deposited in the GitHub repository. Additional public datasets utilized in this study include the human reference genome from 10x Genomics (https://www.10xgenomics.com/support/software/cell-ranger/downloads, refdata-gex-GRCh38-2020-A), TCGA datasets (https://xenabrowser.net/), and scRNA-seq datasets available in the GEO database (Accession Numbers: GSE143423, GSE150660, GSE195861, GSE186344, GSE202501). Source data are provided with this publication.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 3 keywords, 13 MeSH terms, 4 funders, 79 references.

Cite

This paper

Shi, H., Chen, J., Wu, Z., Liu, D.-X., Zhou, J., Wu, X., Yang, A., Li, S., Tai, Y., Jiang, Z., Hu, Z., Zhang, M., Xu, X., Pan, L., & Wang, T. (2026). Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis. Cell death & disease, 17(1), 553. https://doi.org/10.1038/s41419-026-08807-w

BibTeX

@article{shi2026single,
author = {Shi, Haoyuan and Chen, Jiaxin and Wu, Zisheng and Liu, Dong-Xu and Zhou, Jinmei and Wu, Xuexue and Yang, Ailing and Li, Shanhu and Tai, Yanhong and Jiang, Zefei and Hu, Zhiyuan and Zhang, Mingshan and Xu, Xiaojie and Pan, Lu and Wang, Tao},
title = {{Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis}},
journal = {Cell death \& disease},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {553},
publisher = {Nature Publishing Group},
issn = {2041-4889},
doi = {10.1038/s41419-026-08807-w},
url = {https://doi.org/10.1038/s41419-026-08807-w},
pmid = {42034645},
pmcid = {PMC13247122}
}

RIS

TY - JOUR
AU - Shi, Haoyuan
AU - Chen, Jiaxin
AU - Wu, Zisheng
AU - Liu, Dong-Xu
AU - Zhou, Jinmei
AU - Wu, Xuexue
AU - Yang, Ailing
AU - Li, Shanhu
AU - Tai, Yanhong
AU - Jiang, Zefei
AU - Hu, Zhiyuan
AU - Zhang, Mingshan
AU - Xu, Xiaojie
AU - Pan, Lu
AU - Wang, Tao
TI - Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis
T2 - Cell death & disease
J2 - Cell Death Dis
PY - 2026
DA - 2026/04/25
VL - 17
IS - 1
SP - 553
SN - 2041-4889
PB - Nature Publishing Group
DO - 10.1038/s41419-026-08807-w
UR - https://doi.org/10.1038/s41419-026-08807-w
LA - en
ER -

CSL-JSON

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