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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1168-1177
Expression of  4-Integrin Defines the Earliest Precursor of
Hematopoietic Cell Lineage Diverged From Endothelial Cells
Minetaro Ogawa,
Masami Kizumoto,
Satomi Nishikawa,
Tetsuhiro Fujimoto,
Hiroaki Kodama, and
Shin-Ichi Nishikawa
From the Department of Molecular Genetics, Faculty of Medicine, Kyoto
University, Kyoto, Japan; and the Research Center Kyoto, Bayer Yakuhin,
Ltd, Kyoto, Japan.
Embryonic stem cells can differentiate in vitro into hematopoietic
cells through two intermediate stages; the first being FLK1+ E-cadherin proximal lateral mesoderm
and the second being CD45 VE-cadherin+
endothelial cells. To further dissect the CD45
VE-cadherin+ cells, we have examined distribution of
 4-integrin on this cell population, because 4-integrin is the
molecule expressed on hematopoietic stem cells. During culture of
FLK1+ E-cadherin cells,
CD45 VE-cadherin+
4-integrin cells differentiate first, followed by
4-integrin+ cells appearing in both
CD45 VE-cadherin+ and CD45
VE-cadherin cell populations. In the CD45
VE-cadherin+ cell population,
4-integrin+ subset but not
4-integrin subset had the potential to differentiate
to hematopoietic lineage cells, whereas endothelial cell progenitors
were present in both subsets. The CD45
VE-cadherin 4-integrin+ cells also
showed hematopoietic potential. Reverse transcription-polymerase chain
reaction analyses showed that differential expression of the Gata2 and Myb genes correlated with the potential
of the 4-integrin+ cells to give rise to hematopoietic
cell differentiation. Hematopoietic CD45
VE-cadherin+ 4-integrin+ cells were also
present in the yolk sac and embryonic body proper of 9.5 day postcoitum
mouse embryos. Our results suggest that the expression of 4-integrin
is a marker of the earliest precursor of hematopoietic cell lineage
that was diverged from endothelial progenitors.
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