Data from: Single-cell transcriptomic analysis of tumor-derived fibroblasts and normal tissue-resident fibroblasts reveals fibroblast heterogeneity in breast cancer

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in
solid tumors and molecules secreted by CAFs play an important role in
tumor progression and metastasis. CAFs coexist as heterogeneous
populations with potentially different biological functions. Although CAFs
are a major component of the breast cancer stroma, molecular and
phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In
this study, we investigated CAF heterogeneity in triple-negative breast
cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary
tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six
CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs,
enriched for α-smooth muscle actin and several other contractile proteins;
2) ‘inflammatory’ CAFs with elevated expression of inflammatory cytokines;
and 3) a CAF subpopulation expressing major histocompatibility complex
(MHC) class II proteins that are generally expressed in antigen-presenting
cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer
revealed that these three CAF subpopulations exist in both tumor types.
Interestingly, cells with inflammatory and MHC class II-expressing CAF
profiles were also detected in normal breast/pancreas tissue, suggesting
that these phenotypes are not tumor microenvironment-induced. This work
enhances our understanding of CAF heterogeneity, and specifically
targeting these CAF subpopulations could be an effective therapeutic
approach for treating highly aggressive TNBCs.