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Blood, 1 August 2001, Vol. 98, No. 3, pp. 627-635
HEMATOPOIESIS
Fetal liver myelopoiesis occurs through distinct, prospectively
isolatable progenitor subsets
David Traver,
Toshihiro Miyamoto,
Julie Christensen,
Junko Iwasaki-Arai,
Koichi Akashi, and
Irving L. Weissman
From the Departments of Pathology and Developmental Biology,
Stanford University School of Medicine, CA; and the Department of
Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA.
Hematopoietic fate maps in the developing mouse embryo remain
imprecise. Definitive, adult-type hematopoiesis first appears in the
fetal liver, then progresses to the spleen and bone marrow. Clonogenic
common lymphoid progenitors and clonogenic common myeloid progenitors
(CMPs) in adult mouse bone marrow that give rise to all lymphoid and
myeloid lineages, respectively, have recently been identified. Here it
is shown that myelopoiesis in the fetal liver similarly proceeds
through a CMP equivalent. Fetal liver CMPs give rise to
megakaryocyte-erythrocyte-restricted progenitors (MEPs) and
granulocyte-monocyte-restricted progenitors (GMPs) that can also be
prospectively isolated by cell surface phenotype. MEPs and GMPs
generate mutually exclusive cell types in clonogenic colony assays and
in transplantation experiments, suggesting that the lineage restriction
observed within each progenitor subset is absolute under normal
conditions. Purified progenitor populations were used to analyze
expression profiles of various hematopoiesis-related genes. Expression
patterns closely matched those of the adult counterpart populations.
These results suggest that adult hematopoietic hierarchies are
determined early in the development of the definitive immune system and
suggest that the molecular mechanisms underlying cell fate decisions
within the myeloerythroid lineages are conserved from embryo to adult.

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