Gordon Keller, Ph.D.
McEwen Centre for Regenerative Medicine/University Health Network
Division of Stem Cell and Developmental Biology, Ontario Cancer Institute (OCI)
MaRS Centre, 101 College Street TMDT 8-701
Toronto, ON M5G 1L7
Gordon Keller, Ph.D. - Investigator Profile
The focus of my research program is to define and characterize the early events involved in the establishment, growth and maturation of the embryonic hematopoietic and vascular systems. The earliest blood cell precursors of the hematopoietic system as well as the earliest endothelial precursors that will ultimately form the vascular system, develop in structures known as blood islands that can be found in the yolk sac of the mouse embryo at approximately day 7.5 of gestation. The fact that the hematopoietic and endothelial lineages develop in close proximity at precisely the same developmental stage in these blood islands has led to the hypothesis that they develop from a common precursor, a cell known as the hemangioblast. To address questions related to these early stages of lineage commitment, it is important to study the mouse embryo prior to blood island development. As access to the embryo at this stage of development is extremely difficult and the number of cells available limited, we have chosen to study these early events using a model system based on the in vitro differentiation potential of embryonic stem (ES) cells. When ES cells differentiate in culture they generate colonies known as embryoid bodies (EBs) that consist of precursors from multiple lineages including those of the hematopoietic and vascular systems. Previous studies have demonstrated that the establishment of the hematopoietic and endothelial lineages within the EBs parallels that of the embryo with respect to the kinetics of development and differential gene expression patterns. Using the ES differentiation model, we have recently identified a novel precursor that develops early within the EBs and displays the unique capacity to generate cells of both the hematopoietic and endothelial lineages. Given this potential, this cell has the characteristics of the hypothetical hemangioblast, and represents the earliest hematopoietic and endothelial precursor described to- date. Using these early precursors, we have recently carried out a subtractive hybridization between closely staged populations with the aim of identifying genes that are involved in the development of the hemangioblast and the subsequent generation of hematopoietic and endothelial progeny. With this approach, we have isolated a number of novel genes that are expressed at the stage of hemangioblast as well as in the embryonic hematopoietic and endothelial lineages isolated from EBs. The current emphasis of my lab is to define the function of these genes and their role in developmental hematopoiesis and vascular biology.
embryonic hematopoietic and vascular systems