The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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
Show all

Summary, in 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.

Department/s

  • Experimental oncology
  • Division of Translational Cancer Research
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Molecular Cell Biology
  • Tumor Cell Biology
  • Stem Cells and Leukemia
  • Division of Molecular Hematology (DMH)
  • Cancer and matrix remodelling
  • Kidney cancer research group
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2018-12-04

Language

English

Publication/Series

Nature Communications

Volume

9

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology
  • Cancer and Oncology

Status

Published

Research group

  • Experimental oncology
  • Tumor Cell Biology
  • Stem Cells and Leukemia
  • Cancer and matrix remodelling
  • Kidney cancer research group

ISBN/ISSN/Other

  • ISSN: 2041-1723