Mechanisms of dedifferentiation: Linking injury-induced plasticity to cancer initiation
Miguel Bernabé Rubio
King’s College London, UK
The epidermis is a multilayered epithelium that forms the outer covering of the skin. Differentiation occurs as cells move through the suprabasal layers. Epidermal differentiation is irreversible under steady state conditions. However, during wound healing differentiated cells that express the transcription factor Gata6 re-acquire the properties of stem cells in a process known as dedifferentiation. To uncover the underlying mechanism, I integrated lineage tracing with single-cell mRNA-Sequencing. I discovered that dedifferentiation is mediated by the proto-oncogene c-Myc, actin-cytoskeleton remodelling and mechanotransduction. Following injury, the regenerated epidermis appears superficially identical to undamaged epidermis. However, I have discovered that injury-induced tumours arise from dedifferentiated cells. In this presentation I will describe the transcriptional trajectory of dedifferentiation and the influence of this process on cancer initiation.