The control of epithelial/mesenchymal transitional states

Resumen del póster presentado al European Developmental Biology Congress (EDBC), celebrado en Alicante del 23 al 26 de octubre de 2019.Transcription factors that trigger Epithelial-to-Mesenchymal Transition (EMT-TFs) are fundamental for the development of multiple tissues and organs. They can be reactivated in pathological conditions resulting in a profound remodeling of epithelial phenotypes, leading to cancer cell dissemination or functional loss in organ fibrosis. Different EMT-TFs can promote distinct EMT programs and, in addition, both embryonic and cancer cells express different combinations of EMT-TFs. Due to this intrinsic complexity, it is unclear how EMT-TFs are coordinated to orchestrate heterogeneous EMT programs, especially the highly plastic and reversible intermediate or partial EMT (pEMT) states. Here, we used in silico, in vitro and in vivo approaches to decipher the relationship between the expression of different EMT-TFs and the resulting phenotypes. (i) Using in silico analysis, we identify a stereotypic EMT-TFs expression-code accompanying the epithelial, hybrid epithelial/mesenchymal (E-M) and mesenchymal (M) phenotypes. (ii) In cultured epithelial kidney cells, TGF-b-induced EMT can associate with partial or full EMT programmes with a stereotypic EMT-TFs expression code. Manipulation of EMT-TFs expression confirms the sequential recruitment of EMT-TFs to fine-tune EMT states. (iii) In renal fibrosis, an in vivo model of pEMT, damaged tubular epithelial cells acquire a stable pEMT phenotype upon the reactivation of specific EMT-TFs, and reminiscent of E-M hybrid phenotype profile identified in our in silico and in vitro analyses. In summary, this work provides evidence for specific combinatorial EMT-TFs codes that regulate the heterogeneity and plasticity of EMT programs leading to different pathological outcomes.Peer reviewe