aSMA+ fibroblasts suppress differentiation of Lgr5+ cancer stem cells via BMP4 and restrain progression of colorectal cancer

Purpose: This study interrogated the role of aSMA+ CAFs in a genetic moue model of metastatic colorectal cancer. Methods: aSMA+ CAFs were selectively depleted in mouse CRC model. RNA was isolated from tumors from control and depleted mice, as well as from the colon of WT mice and sequenced. Results: Mice with aSMA+ CAF-depletion exhibited increased inflammation and immunosuppressive phenotype in tumors. Depleted mice also had an increased incidence of Lgr5+ CSCs. BMP4 and TGFß1 was increased in depleted tumors compared to control. Conclusion: aSMA+ CAFs have a tumor restraining function in CRC, via BMP4/TGFß1 signaling. Overall design: Total RNA sequenced from tumors from 3 control and 3 depleted mice, as well as normal colon epithelium from 3 WT mice.