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 Blood, 15 April 2008, Vol. 111, No. 8, pp. 4055-4063.
Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-05-091710.

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HEMATOPOIESIS AND STEM CELLS

Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues

Vanta J. Jokubaitis1,2, Lidia Sinka3,4, Rebecca Driessen1, Genevieve Whitty5, David N. Haylock5, Ivan Bertoncello5, Ian Smith6, Bruno Péault7, Manuela Tavian3,4, and Paul J. Simmons1,8

1 Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia; 2 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia; 3 Inserm U602, Villejuif, France; 4 Universite Paris-Sud, Faculte de Medecine, Villejuif, France; 5 Australian Stem Cell Centre, Clayton, Australia; 6 Baker Institute, Prahran, Australia; 7 Rangos Research Center, Children's Hospital, Pittsburgh, PA; and 8 Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Center, Houston, TX

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.


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