Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues.
Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map BB9 expression throughout hematopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and surrounding endothelial cells are BB9(+). Thereafter, BB9 is expressed by primitive hematopoietic cells in fetal liver and in umbilical cord blood (UCB). BB9(+)CD34(+) UCB cells transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice contribute 10-fold higher numbers of multilineage blood cells than their CD34(+)BB9(-) counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34(+) population. Protein microsequencing of the 160-kDa band corresponding to the BB9 protein established its identity as that of somatic angiotensin-converting enzyme (ACE). Although the role of ACE on human HSCs remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSCs throughout hematopoietic ontogeny and adulthood.
Jokubaitis
Vanta J
VJ
Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Sinka
Lidia
L
Driessen
Rebecca
R
Whitty
Genevieve
G
Haylock
David N
DN
Bertoncello
Ivan
I
Smith
Ian
I
Péault
Bruno
B
Tavian
Manuela
M
Simmons
Paul J
PJ
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000187:drug effects; D018952:Antigens, CD34 / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006413:Hematopoietic System / Q000196:embryology / Q000201:enzymology*; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A