Single cell and spatial sequencing analysis of cancer associated fibroblasts in the brain metastasis tumor microenvironment [Multiome]

Cancer-associated fibroblasts (CAFs) can either support or inhibit tumor growth in the tumor microenvironment (TME), yet their roles in BM remain under-described. Here we report a single-cell and spatial sequencing analysis of human BM tissues and define four transcriptionally distinct CAF subpopulations.

BM CAF subpopulations are characterized by either extracellular matrix (ECM), immune, contractile, or neural features, and show distinct spatial distributions within the BM TME. Further analyses reveal that BM CAFs engage extensively in cell-cell communication and adopt distinct cell states, including an ECM CAF cell state marked by high levels of immunoglobulin superfamily containing leucine rich repeat expression (ISLR-CAFs).