Fig. 7

Overview of collagen type I-dependent epithelial cell plasticity. Schematic illustration how collagen type I triggers epithelial cell fate conversion in both mouse and human cells is presented. Collagen type I stimulates integrin a2b1 heterodimers, subsequently promotes nuclear translocation of YAP/TAZ. In the nuclear, YAP/TAZ coordinates with Fra1 and Runx2 to induce fetal marker genes such as Ly6a/Clu/Tacstd2 in mouse and TACSTD2 in human. Genes involved in YAP module such as Tead/Wwtr1 are also induced, which will be subsequently recruited into the cascade to form a positive feedback loop. Downstream of the cascade, various responses are initiated, including the production of inflammatory molecules PTGS2, cytokine secretion such as IL33 and IL18, cytoskeletal organization with several different types of keratins such as KRT80, complements production such C4BPB, and ECM secretion such as collagen type IV and fibronectin. ECM secretion will subsequently remodel the ECM-niche and will influence the cascade