Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10721 (
c-kit
)
6,575
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified
endothelial cell-selective adhesion molecule
(
ESAM
) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1(-)
c-kit
(Hi) Sca1(+) HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of
ESAM
levels. Among endothelial antigens on hematopoietic progenitors,
ESAM
expression showed intimate correlation with HSC activity. The
ESAM
(Hi) population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2(+)
c-kit
(+) lymphohematopoietic cells in the E9.5-10.5 aorta-gonad-mesonephros region also expressed high levels of
ESAM
. Furthermore,
ESAM
was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly,
ESAM
expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that
ESAM
marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.
...
PMID:The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice. 1932 7
Hematopoietic stem cell-containing intra-aortic hematopoietic cell clusters (IAHCs) emerge in the dorsal aorta of the aorta-gonad-mesonephros (AGM) region during midgestation mouse embryos. We previously showed that transduction of Sox17 in CD45
low
c-Kit
high
cells, which are one component of IAHCs, maintained the cluster formation and the undifferentiated state, but the mechanism of the cluster formation by Sox17 has not been clarified. By microarray gene expression analysis, we found that genes for vascular endothelial-cadherin (VE-cad) and
endothelial cell-selective adhesion molecule
(
ESAM
) were expressed at high levels in Sox17-transduced
c-Kit
+
cells. Here we show the functional role of these adhesion molecules in the formation of IAHCs and the maintenance of the undifferentiated state by in vitro experiments. We detected VE-cad and
ESAM
expression in endothelial cells of dorsal aorta and IAHCs in E10.5 embryos by whole mount immunohistochemistry. Cells with the middle expression level of VE-cad and the low expression level of
ESAM
had the highest colony-forming ability. Tamoxifen-dependent nuclear translocation of Sox17-ERT fusion protein induced the formation of cell clusters and the expression of Cdh5 (VE-cad) and
ESAM
genes. We showed the induction of the Cdh5 (VE-cad) and
ESAM
expression and the direct interaction of Sox17 with their promoter by luciferase assay and chromatin immunoprecipitation assay, respectively. Moreover, shRNA-mediated knockdown of either Cdh5 (VE-cad) or
ESAM
gene in Sox17-transduced cells decreased the multilineage-colony forming potential. These findings suggest that VE-cad and
ESAM
play an important role in the high hematopoietic activity of IAHCs and cluster formation.
...
PMID:Sox17-mediated expression of adherent molecules is required for the maintenance of undifferentiated hematopoietic cluster formation in midgestation mouse embryos. 3289 59
