Tosato – Feng – 2023

Madeline GinerStudy of the contribution of endothelial cells to adult hematopoiesis 

Hematopoiesis is the process by which all blood cells are produced. In the adult mouse, hematopoiesis occurs predominantly in the bone marrow where the hematopoietic stem cells (HSC) reside and differentiate into all mature blood cells that are released into the circulation when needed. The HSC, at the top of the hierarchical hematopoietic system, are produced by specialized endothelial cells through a process of endothelial-to-hemogenic transition (ENT) during mouse development. HSC produced during development are generally believed to sustain hematopoiesis thought adult life. Endothelial cells in the adult bone marrow contribute to sustain the HSC by producing critical growth factors and providing other forms of support acting through specialized units called “niches”, which represents geographically defined functional units in the bone marrow. We are interested in two aspects of the endothelial cell contribution to hematopoiesis. First, we are interested in exploring the possibility that specialized endothelial cells in the adult bone marrow can undergo adult EHT and produce HSC in certain circumstances. This would provide a much-needed new source of blood cells. Second, we are interested in better defining bone marrow endothelial cell niche function for HSC, which are still incompletely defined. We use a variety of experimental approaches to advance research, including genetic, epigenetic, and biochemical approaches to study genes, gene expression, mRNA translation, and proteins; we use a variety of cell-based systems and mouse models of hematopoiesis. The student will be paired with a post-doctoral fellow in the laboratory and will work under supervision to the extent necessary with the goal of making the experience valuable for the student.