M. Ogawa et al., Expression of alpha 4-integrin defines the earliest precursor of hematopoietic cell lineage diverged from endothelial cells, BLOOD, 93(4), 1999, pp. 1168-1177
Embryonic stem cells can differentiate in vitro into hematopoietic cells th
rough two intermediate stages; the first being FLK1(+) E-cadherin(-) proxim
al lateral mesoderm and the second being CD45(-) VE-cadherin(+) endothelial
cells. To further dissect the CD45(-) VE-cadherin(+) cells, we have examin
ed distribution of alpha 4-integrin on this cell population, because alpha
4-integrin is the molecule expressed on hematopoietic stem cells. During cu
lture of FLK1(+) E-cadherin(-) cells, CD45(-) VE-cadherin(+) alpha 4-integr
in(-) cells differentiate first, followed by alpha 4-integrin(+) cells appe
aring in both CD45- VE-cadherin+ and CD45(-) VE-cadherin(-) cell population
s. In the CD45(-) VE-cadherin(+) cell population, alpha 4-integrin(+) subse
t but not alpha 4-integrin(-) subset had the potential to differentiate to
hematopoietic lineage cells, whereas endothelial cell progenitors were pres
ent in both subsets. The CD45(-) VE-cadherin(-) alpha 4-integrin(+) cells a
lso 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 giv
e rise to hematopoietic cell differentiation. Hematopoietic CD45(-) VE-cadh
erin(+) alpha 4-integrin(+) cells were also present in the yolk sac and emb
ryonic 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: precu
rsor of hematopoietic cell lineage that was diverged from endothelial proge
nitors. (C) 1999 by The American Society of Hematology.