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Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing

Author:
  • Michael Bartoschek
  • Nikolay Oskolkov
  • Matteo Bocci
  • John Lövrot
  • Christer Larsson
  • Mikael Sommarin
  • Chris Madsen
  • David Lindgren
  • Gyula Pekar
  • Göran Karlsson
  • Markus Ringnér
  • Jonas Bergh
  • Åsa K. Björklund
  • Kristian Pietras
Publishing year: 2018-12-04
Language: English
Publication/Series: Nature Communications
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium. Gene profiles for each CAF subtype correlate to distinctive functional programs and hold independent prognostic capability in clinical cohorts by association to metastatic disease. In conclusion, the improved resolution of the widely defined CAF population opens the possibility for biomarker-driven development of drugs for precision targeting of CAFs.

Keywords

  • Cell and Molecular Biology
  • Cancer and Oncology

Other

Published
  • Experimental oncology
  • Tumor Cell Biology
  • Stem Cells and Leukemia
  • Cancer and matrix remodelling
  • Kidney cancer research group
  • ISSN: 2041-1723
Markus Ringnér
E-mail: markus [dot] ringner [at] biol [dot] lu [dot] se

Research engineer

Molecular Cell Biology

B-A317

Sölvegatan 35, Lund

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