Fig. 1

The mesenchymal niche populations at the peri-crypt regions of the normal and diseased colon in mice. Left panel. During normal homeostasis, there are three main cellular sources of niche signals for colonic stem cells (SC): the Reg4⁺ deep crypt secretory cells from the epithelial compartment, and the telocyte and trophocyte populations from the mesenchyme compartment. Middle panel. During AOM-induced tumorigenesis, a rare population of peri-cryptal PTGS2-expressing fibroblast (RPPF) cells appears and communicates directly with the adjacent tumor-initiating stem cell (TISC) via a PGE2-PTGER4-YAP signaling axis to promote TISC proliferation and tumorigenesis. Right panel. In DSS-treated colon, a stromal cell population termed as MRISC appears at the bottom of the crypt base that produces Rspo1 via a ROS-MAP3K2-ERK5-KLF2-Rspo1 signaling cascade to promote self-renewal of colonic stem cells, thereby exerting a protective effect against inflammation-induced colonic damage