Molecular mechanisms that regulate hemogenic endothelial cells in the mouse embryo

Abstract

Production of blood cells (hematopoiesis) is critical for embryonic survival. In mouse concepti, hematopoietic development is characterized by waves of activity that result in the production of different blood cell types. Definitive hematopoietic cells are derived from a specialized subset of endothelial cells that line the inner aspect of blood vessels. Endothelial cells with hematopoietic potential are called ‘hemogenic’. These specialized cells can only be found in a few embryonic tissues during a narrow developmental window. Through a process called endothelial-to-hematopoietic transition, endothelial cells with adherens junctions generate free-floating blood cells. However, the mechanisms that regulate hemogenic activity and definitive hematopoiesis are not entirely clear. The aims of this thesis are to further characterize hemogenic and non-hemogenic niches of mouse concepti and to better understand hemogenic endothelial specification and definitive hematopoietic development. Our work revealed critical developmental times in hematopoietic regulation and showed that different genes are required in a temporally-regulated manner across distinct tissues of the conceptus. We also revealed new candidates that could be involved in definitive hematopoietic regulation during embryonic development. Together with other developmental studies, our research provides information that can potentially be used to develop new therapies to treat blood disorders.