Expression of α4-integrin defines the earliest precursor of hematopoietic cell lineage diverged from endothelial cells

被引:79
作者
Ogawa, M
Kizumoto, M
Nishikawa, S
Fujimoto, T
Kodama, H
Nishikawa, SI
机构
[1] Kyoto Univ, Fac Med, Dept Mol Genet, Sakyo Ku, Kyoto 60685807, Japan
[2] Bayer Yakuhin Ltd, Res Ctr Kyoto, Kyoto, Japan
关键词
D O I
10.1182/blood.V93.4.1168.404k12_1168_1177
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 alpha 4-integrin on this cell population, because alpha 4-integrin is the molecule expressed on hematopoietic stem cells. During culture of FLK1(+) E-cadherin(-) cells, CD45(-) VE-cadherin(+) alpha 4-integrin(-) cells differentiate first, followed by alpha 4-integrin(+) cells appearing in both CD45- VE-cadherin+ and CD45(-) VE-cadherin(-) cell populations. In the CD45(-) VE-cadherin(+) cell population, alpha 4-integrin(+) subset but not alpha 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(-) alpha 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 alpha 4-integrin(+) cells to give rise to hematopoietic cell differentiation. Hematopoietic CD45(-) VE-cadherin(+) alpha 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 alpha 4-integrin is a marker of the earliest: precursor of hematopoietic cell lineage that was diverged from endothelial progenitors. (C) 1999 by The American Society of Hematology.
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页码:1168 / 1177
页数:10
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