SSA - Defining the stromal cell subtypes controlling bone homeostasis and haematopoiesis.

Adult mesenchymal stem cells (MSCs) are located in bone marrow and are able to differentiate into bone, cartilage and fat to support the maintenance and repair of the skeleton. There is ample evidence that MSCs are also able to control other aspects of marrow function, but progress has been hampered as MSCs are difficult to distinguish from other stromal cell types because they lack specific identifying markers. We have generated a panel of immortalised, single cell-derived MSC lines to enable in-depth analysis of MSC subtype function with specific, distinguishing characteristics. These MSC lines display widely variable differentiation competencies but we have not explored other MSC functions including how they support haematopoietic cell behaviour and the production of different blood cell types, as well as immunoregulatory behaviour. This project will make use of this unique MSC resource to determine how MSC subtypes contribute to the support of haematopoietic stem cells and their differentiation into specific cell types. We will use screening techniques to identify novel MSC markers combined with in vivo studies to determine niche compositions and location. Collectively, this work will unveil previously unrecognised cell-cell interactions that determine stem cell behaviour across different lineages.