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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4160-4168
HEMATOPOIESIS
During ontogeny primitive (CD34+CD38 )
hematopoietic cells show altered expression of a subset of genes
associated with early cytokine and differentiation responses of
their adult counterparts
Il-Hoan Oh,
Aster Lau, and
Connie J. Eaves
From the Terry Fox Laboratory, British Columbia Cancer
Agency and Department of Medical Genetics, University of British
Columbia, Vancouver, BC, Canada.
Comparison of gene expression profiles in closely related
subpopulations of primitive hematopoietic cells offers a powerful first
step to elucidating the molecular basis of their different biologic
properties. Here we present the results of a comparative quantitative
analysis of transcript levels for various growth factor receptors,
ligands, and transcription factor genes in
CD34+CD38 and
CD34+CD38+ cells purified from first trimester
human fetal liver, cord blood, and adult bone marrow (BM). In addition,
adult BM CD34+CD38 cells were examined after
short-term exposure to various growth factors in vitro. Transcripts for
19 of the 24 genes analyzed were detected in unmanipulated adult BM
CD34+CD38 cells. Moreover, the levels of
transforming growth factor beta (TGF- ), gp130, c-fos,
and c-jun transcripts in these cells were consistently and
significantly different (higher) than in all other populations
analyzed, including phenotypically similar but biologically different
cells from fetal or neonatal sources, as well as adult BM
CD34+ cells still in G0 after 2 days of growth
factor stimulation. We have thus identified a subset of early response
genes whose expression in primitive human hematopoietic cells is
differently regulated during ontogeny and in a fashion that is
recapitulated in growth factor-stimulated adult BM
CD34+CD38 cells, before their cell cycle
progression and independent of their subsequent differentiation
response. These findings suggest a progressive alteration in the
physiology of primitive hematopoietic cells during development such
that these cells initially display a partially "activated" state,
which is not maximally repressed until after birth.
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