Keller, Gordon

GORDON M. KELLER is the senior scientist in the Division of Stem Cell and Developmental Biology at the Ontario Cancer Institute. He is also the director of the McEwen Centre for Regenerative Medicine and works at the MaRS Center in the Toronto Medical Discovery Tower in Canada. He also holds the Canada Research Chair in embryonic stem biology.

Keller's research interests are in the areas of lineage—specific differentiation of embryonic stem (ES) cells in culture; development of hematopoietic, vascular, and cardiac lineages from ES cells; commitment of ES cells to endoderm—derived lineages; and growth and differentiation of human embryonic stem cells. More specifically, Keller is focused on a research program that is seeking to define and to describe fully the essentials of the process of embryonic development. He is seeking to understand the early events that are part of the process of the establishment, growth, and maturation of the embryonic hematopoietic and vascular system.

Hematopoiesis is the process that results in the formation of blood cellular components. The cells involved are multipotent because they have the [Page 287]ability to become a number of different types of cells. They are not, however, germ cells, which are part of the reproductive process. Specifically, any type of cell found in the blood system can be made from the multipotent hematopoietic cells. The rate of production of cells in the blood system is at a relatively high rate, so great numbers of these cells are continually being made.

Identifying and understanding the earliest blood cell precursors of the hematopoietic system will aid in the development of treatments. There are also endothelial precursors involved. These precursors form the vascular system, and develop into structures known as blood islands. These islands can be found in the yolk sac of the mouse embryo and develop after 7.5 days of gestation.

The development of hematopoietic and endothelial lineages in near simultaneity in the blood islands is a kind of scientific platform. From it, Keller has hypothesized that both of these lineages are developing from a progenitor cell that has issued a series of commands for development. The progenitor cell is called the hemangioblast. Understanding the nature of the hemangioblast is very important because doing so will answer questions about the early stages of lineage commitment.

Studying mouse embryos before blood island development is an important part of the current research. It is extremely difficult to gain access to the mouse embryo at fewer than seven days because there are just a few cells available. To study the very early events, Keller has developed a model that is based on the in vitro potential of ES cells.

Keller and others have found that as ES cells differentiate in cultures, they generate colonies that have been labeled embryoid bodies (EBs). These bodies consist of the precursors from multiple lineages, including those of the hematopoietic and vascular systems. From earlier studies, it is known that as the embryo develops, it establishes both the hematopoietic and the endothelial lineages. What happens within the EB parallels the kinetics of development as well as the differential gene expression patterns.

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