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Mammalian homeobox B6 expression can be correlated with erythropoietin
production sites and erythropoiesis during development, but not with
hematopoietic or nonhematopoietic stem cell populations
F Zimmermann and IN Rich
Department of Transfusion Medicine, University of Ulm, Germany.
There has been increasing interest in the involvement of mammalian homeobox
(HOX) genes in hematopoietic regulation. The HOX genes are clustered in 4
chromosomes in mice and humans. In general, 5' end HOX gene expression is
predominant in hematopoietic stem cell populations, whereas 3' end HOX gene
expression are primarily found in committed progenitor cells. Furthermore,
HOX genes of the A cluster are generally found in myelomonocytic cells, B
cluster genes in erythropoietic cells, and C cluster genes in lymphoid
cells. The results presented here concentrate on a single gene, namely HOX
B6. Preliminary observations using whole mount in situ hybridization showed
that both HOX B6 and erythropoietin (EPO) gene expression occurred in
exactly the same areas of the 8.5-day mouse embryo. As a consequence, we
studied the expression of HOX B6 and EPO gene expression from 6.5 to 19.5
days of gestation, in the neonate, and in the adult. It was found that the
sequential transfer of erythropoiesis in different organs during
development was followed by a similar transfer of HOX B6 and EPO gene
expression. Between days 16.5 and 17.5, both HOX B6 and EPO gene expression
decrease in the fetal liver, even though hepatic erythropoiesis continues
to decline and is transferred to the fetal spleen. Precisely at this time
point, HOX B6 and EPO gene expression are transferred to both the fetal
spleen and fetal kidney. However, surprisingly, expression of both genes
increases again in the fetal liver just before birth. HOX B6 is expressed
in cells from in vitro erythropoietic colonies (colony-forming
unit-erythroid and burst- forming unit-erythroid) and TER-119+ erythroid
cells but not in hematopoietic or nonhematopoietic stem cell populations.
When the latter two populations are allowed to differentiate into
erythropoietic cells, HOX B6 and erythroid-relevant markers are expressed.
The results indicate that HOX B6 is intimately involved in the regulation
of the erythropoietic system and could be a marker for this lineage.
Volume 89,
Issue 8,
pp. 2723-2735,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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