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 Blood, 9 July 2009, Vol. 114, No. 2, pp. 268-278.
Prepublished online as a Blood First Edition Paper on May 6, 2009; DOI 10.1182/blood-2008-12-193888.

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HEMATOPOIESIS AND STEM CELLS

Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells

Shannon L. McKinney-Freeman13, Olaia Naveiras13, Frank Yates1,4, Sabine Loewer13, Marsha Philitas1,2,5, Matthew Curran13, Peter J. Park6, and George Q. Daley13,5

1 Division of Pediatric Hematology/Oncology, Manton Center for Orphan Diseases, Stem Cell Transplantation Program, Children's Hospital, Boston, MA; 2 Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA; 3 Harvard Stem Cell Institute, Cambridge, MA; 4 Human Embryonic Stem Cell Core Facility, Hopital Paul Brousse, Villejuif, France; 5 Howard Hughes Medical Institute, Chevy Chase, MD; and 6 Children's Hospital Informatics Program, Boston, MA

Surface antigens on hematopoietic stem cells (HSCs) enable prospective isolation and characterization. Here, we compare the cell-surface phenotype of hematopoietic repopulating cells from murine yolk sac, aorta-gonad-mesonephros, placenta, fetal liver, and bone marrow with that of HSCs derived from the in vitro differentiation of murine embryonic stem cells (ESC-HSCs). Whereas c-Kit marks all HSC populations, CD41, CD45, CD34, and CD150 were developmentally regulated: the earliest embryonic HSCs express CD41 and CD34 and lack CD45 and CD150, whereas more mature HSCs lack CD41 and CD34 and express CD45 and CD150. ESC-HSCs express CD41 and CD150, lack CD34, and are heterogeneous for CD45. Finally, although CD48 was absent from all in vivo HSCs examined, ESC-HSCs were heterogeneous for the expression of this molecule. This unique phenotype signifies a developmentally immature population of cells with features of both primitive and mature HSC. The prospective fractionation of ESC-HSCs will facilitate studies of HSC maturation essential for normal functional engraftment in irradiated adults.


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