Pericytes in hematopoietic and heart development and injury

To date, hematopoietic stem cells (HSCs) cannot be generated and expanded ex vivo. In vivo, HSCs generate from hemogenic endothelial cells from the dorsal embryonic aorta and this requires intrinsic and extrinsic factors from the surrounding microenvironment. The cellular composition of the microenvironment is unknown. It comprises endothelial cells and mesenchymal cells. Our hypothesis is that pericytes and other perivascular mesenchymal cells have distinct roles in hematopoietic development and that a subset of pericytes is required to generate HSCs. They may have an intrinsic genetic programme or establish a particular cell contact with endothelial cells which dictate, in time and space, the birth of HSCs. To address this question, we genetically manipulate pericytes and other perivascular cells in the immediate vicinity of hemogenic endothelial cells to disrupt HSC generation in vivo. Using similar strategies, we test whether pericytes play a role in the heart repair process and regeneration upon injury at adult stage. Finally, we aim to understand what is/are the origin(s) of pericytes during mouse development. We use in the lab state-of-the-art technologies such as confocal imaging, live imaging, transgenic mice, cre-lox system as well as transcriptome and metabolome in close collaboration with other groups. Our work has implications in both leukemia and myocardium infarct.