Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity

Intestinal stem cells (ISCs) are adult multipotent cells essential for the maintenance of intestinal epithelial homeostasis. Wnt signaling activity ensures that the pool of ISCs at the basis of the intestinal crypts is preserved. Dysregulation of the Wnt pathway is often observed in cancer and supports malignant progression. Chiacchiera and colleagues recently demonstrated the implication of the polycomb complex PRC1 in the regulation of the Wnt pathway in adult ISCs. The authors show that PRC1 maintains intestinal homeostasis by repressing the expression of ZICs, a family of transcription factors inactivating the β-catenin/TCF complex. Importantly, interfering with PRC1 activity completely inhibits the formation of Wnt-dependent tumors. These findings reveal a new layer of epigenetic regulation of the Wnt pathway and open novel opportunities for cancer stem cell targeted therapy.