Project 461676

Mesenchymal progenitors (MPs) are a type of stem/progenitor cell and are present to varying extents in all tissues of our bodies. Under normal conditions, these cells are in a quiet state and are considered to be quiescent. Quiescence is a defining and vital property of many stem and progenitor cells, and this feature is critical to the healthy maintenance, renewal and regeneration of tissues. MPs exit quiescence and become activated following injury due to trauma (or inflammation, disease and other signals), and this is associated with an expansion of the MP population. Activated MPs serve a number of critical and diverse roles, supporting tissue regeneration and directly contributing to healed tissue. Following successful regeneration, a subset of the activated cells returns to a quiescent state, ready to participate in future renewal/regenerative events. In other instances, activated MPs endure, and contribute to tissue repair and cause fibrosis, which is associated with the accumulation of scar tissue that typically impairs organ function. Fibrosis underlies ~45% of chronic diseases and is a major contributor to the functional decline of organs. A series of novel genetic models will be used to explore the contribution of MPs to fibrosis, with a specific emphasis on the development of therapeutic approaches to modify MP activity to reduce fibrosis. In short, MPs have broad and vital roles in many aspects of health and disease. A better understanding of the processes which regulate their quiescence and activation are expected to lead to novel insights into the molecular and cellular basis of a spectrum of diseases. This information will also support the development of new therapeutics aimed at modifying MP behavior, in order to improve tissue regeneration and reduce fibrosis.