| Summary: | CD34 is a cell surface sialomucin expressed by hematopoietic stem cells
(HSC) and vascular endothelia and is widely used for the enrichment of
human hematopoietic stem cells because of its selective expression on
progenitor cells and absence on mature hematopoietic cells. Although
CD34 was undetectable in all murine progenitor cell lines tested, high
expression was detected in bone marrow-derived mast cells (BMMC) and
in peritoneal mast cells analyzed in vivo. Our results demonstrate that,
contrary to current dogma, CD34 is expressed by one mature
hematopoietic lineage: mast cells. Our data also demonstrate that
antigenically, murine mast cells, and their precursors, closely resemble
HSC. However, in contrast, human CD34 is not expressed by human
mast cells, and this dichotomy represents a regulatory difference for this
protein between these two species.
Despite its popularity as an HSC marker, the function of CD34 on
hematopoietic cells remains enigmatic. Here I have addressed this
issue by examining the behavior of mutant mast cells lacking CD34,
the related sialomucin, CD43, or both molecules. Loss of these
molecules leads to a gene-dose-dependent increase in mast cell
homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild type. Importantly, re-expression of CD34 or CD43 in these cells
caused reversal of this phenotype. Furthermore, I found that loss of
these sialomucins prevented mast cell repopulation and hematopoietic
precursor reconstitution in W/W[sup v] recipients. However, the ability of
these cells to reconstitute lethally irradiated wild type mice is not
impaired, presumably due to irradiation induced differences within the
host. Our data provide the first clear-cut evidence for a hematopoietic
function for CD34 and suggest that it acts as a negative regulator of
cell adhesion. === Medicine, Faculty of === Medical Genetics, Department of === Graduate
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