Definitive hematopoietic commitment within the embryonic vascular endothelial-cadherin(+) population.
OBJECTIVE
The aim of this study was to assess the potential of FLK1(+) and vascular endothelial (VE)-cadherin(+) populations from different stages of embryonic development to generate hematopoietic cells ex vivo and to contribute to the hematopoietic systems of recipient mice.


METHODS
FLK1(+) of VE-cadherin(+) cells were isolated from 7.5- to 9.5-dpc concepti and cultured ex vivo on OP9 stromal cells and hematopoietic development examined. VE-cadherin(+)CD45(-) cells from 8.5- and 9.5-dpc concepti were injected intrahepatically into newborn busulfan-treated SCID recipients and engraftment monitored.


RESULTS
VE-cadherin(+) cells from 7.5- and 8.5-dpc concepti can readily generate hematopoi-etic cells ex vivo compared to FLK1(+) VE-cadherin(-) cells. Similar hematopoietic potential can be found in the VE-cadherin(+) cells from the 8.5-dpc yolk sac. When VE-cadherin(+)CD45(-) cells were injected into SCID recipients, long-term engraftment, particularly within the lymphoid system, was observed. This potential was observed in VE-cadherin(+)CD45(-) cells from 9.5-dpc embryo or yolk sac but from tissues from younger concepti.


CONCLUSIONS
FLK1(+)VE-cadherin(-) cells, possibly representing the lateral plate mesoderm, are not as effective at generating hematopoietic cells compared to similarly staged VE-cadherin(+) cells. VE-cadherin(+)CD45(-) cells can also contribute to the hematolymphoid system of intrahepatically injected newborn SCID recipients, suggesting that cells bearing an endothelial phenotype are capable of generating long-term hematopoietic precursors.
Fraser
Stuart T
ST
Department of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto, Japan. sfraser@virus1.virus.kyoto-u.ac.jp
Ogawa
Minetaro
M
Yu
Ruth T
RT
Nishikawa
Satomi
S
Yoder
Mervin C
MC
Nishikawa
Shin-Ichi
S
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD; D001854:Bone Marrow Cells / Q000166:cytology; D015820:Cadherins / Q000032:analysis*; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology; D002678:Chimera; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D005865:Gestational Age; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006413:Hematopoietic System / Q000196:embryology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*; D015017:Yolk Sac / Q000166:cytology; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D017493:Leukocyte Common Antigens; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5