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Pediatrics Department

Aab Institute

Summary of Research Interests:

Hematopoietic stem cells responsible for the production of blood cells throughout life arise during embryogenesis. However, the mechanisms that initiate blood cell development are largely unknown. The long-term aim of our laboratory is to elucidate the cellular and molecular events underlying the initiation of hematopoiesis in the mammalian embryo. The first hematopoietic cells to emerge during mammalian embryogenesis are “primitive” red cells that are necessary for survival of the fetus. Our recent studies indicate that the primitive erythroid lineage in mice as "mammalian", rather than "non-mammalian" in character. Primitive erythropoiesis will thus serve as an important model of mammalian erythroid differentiation. Since differential gene expression precedes morphologic changes during embryogenesis, we determined the temporal and spatial expression patterns of hematopoietic transcription factors in the mouse embryo. We have also analyzed the ontogeny of unipotential and multipotential hematopoietic progenitors during post-implantation mouse embryogenesis. These studies point to early gastrulation and extra-embryonic mesoderm as the initial time and place of hematopoietic lineage specification from a hemangioblast precursor. Two waves of hematopoietic precursors have been identified in the yolk sac prior to colonization of the liver and the lineage composition and relationships of these primitive and definitive precursor waves are under active investigation. Our studies indicate that the onset of hematopoiesis within the yolk sac of mammals is much more complex than previously thought.

An understanding of the initiation of mammalian hematopoiesis will ultimately produce insights into the ontogeny, regulation and expansion of hematopoietic stem cells. These insights will lead to a better understanding of genetic disorders, bone marrow failure syndromes and leukemias. They will also lead to improvements in bone marrow transplantation for the curative treatment of numerous congenital anemias, genetic diseases, and several forms of childhood and adult cancers.

The Palis laboratory is a collaborative team that includes Paul Kingsley Ph.D., Kathleen McGrath Ph.D., Anne Koniski MA, Jeff Malik, Rachael Emerson, and Joanna Tober (graduate student).

Recent Publications:

1. Huber TL, Kouskoff V, Fehling HJ, Palis J, Keller G. Hemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 432:625-630, 2004

2. Kingsley PD , Malik J, Fantauzzo KA, Palis J. Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis. Blood 104:19-25, 2004

3. McGrath KE, Koniski AD, Malik J, Palis J. Circulation is established in a step-wise pattern in the mammalian embryo. Blood 101:1669-1676, 2003

4. Palis J, Chan RJ, Koniski A, Patel R, Starr M, Yoder MC. Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis. Proc Natl Acad Sci USA 98:4528-4533, 2001

5. Palis J, Kennedy M, Robertson S, Wall C, Keller G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse embryo. Development 126:5073-5084, 1999

LAST MODIFIED: Jan 2005
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