| 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 my laboratory is
to elucidate the molecular events underlying the initiation
of hematopoiesis in the mammalian embryo. Since differential
gene expression precedes morphologic changes during embryogenesis,
we have performed in situ hybridization studies of hematopoietic
transcription factors in the mouse embryo. These studies point
to extraembryonic mesoderm and early gastrulation as the initial
time and place of hematopoietic specification. We have determined
that the yolk sac is the first site of unipotential and multipotential
hematopoietic progenitors which give rise to the embryo’s
first mature blood cells and the precursors that will seed
the fetal liver. Collaborative efforts are ongoing to investigate
the embryologic origin of hematopoietic stem cells.
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.
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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 1999;126:5073-5084.
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.
Proceedings National Academy of Science USA 2001;98:4528-4533.
McGrath KE, Koniski AD, Malik J, Palis J: Circulation
is established in a step-wise pattern in the mammalian embryo.
Blood 2003;101:1669-1676.
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