biostudies-literatureFriedman GCancer Research UKEuropean Research CouncilHoward Hughes Medical InstituteNational Institute for Health Research (NIHR)692-708https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617059biostudies-literatureUnknown1(7)Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is asNature cancerCancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4<sup>+</sup> and PDPN<sup>+</sup> CAFs to clinical outcome.PMC76170592581529567724471C19767/A2714575432027145A_CRI_1920_AliCL-2013-14-006Ali HRDadiani MNevo RScherz-Shouval RDavid EBarshack IPevsner-Fischer MBornstein CGiladi ACaldas CAlon UHalperin CFriedman GLevi-Galibov OBalint-Lahat NLavon HStein YMayer SAmit INili-Gal-Yam EMayo AfalseCancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4<sup>+</sup> and PDPN<sup>+</sup> CAFs to clinical outcome.Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is as2020-01-01T00:00:00Z2020 Jul2025-04-21T21:47:54.139Z2025-04-21T21:47:54.139ZS-EPMC76170593512204010.1038/s43018-020-0082-y