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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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Submitted May 22, 2007
Accepted October 15, 2007
Angiotensin-Converting Enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal and adult hematopoietic tissues
Vanta J Jokubaitis, Lidia Sinka, Rebecca Driessen, Genevieve Whitty, David N Haylock, Ivan Bertoncello, Ian Smith, Bruno Peault, Manuela Tavian, and Paul J Simmons*
Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
INSERM U602, Villejuif, France
Australian Stem Cell Centre, Clayton, Victoria, Australia
Research Laboratory, Baker Institute, Prahran, Victoria, Australia
Rangos Research Center, Children's Hospital, Pittsburgh, PA, United States
Faculte de Medecine, Universite Paris-Sud, Villejuif, France
Brown Foundation Institute of Molecular Medicine (IMM), University of Texas Health Science Centre, Houston, TX, United States
* Corresponding author; email: paul.j.simmons{at}uth.tmc.edu.
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 HSC 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 NOD/SCID mice contribute 10-fold higher numbers of multi-lineage blood cells than their CD34+BB9- counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34+ population. Protein micro-sequencing of the 160kDa band corresponding to the BB9 protein established its identity as that of somatic Angiotensin Converting Enzyme (ACE). Although the role of ACE on human HSC remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSC throughout hematopoietic ontogeny and adulthood.
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