Published online 4 July 2008
Haematologica, Vol 93, Issue 8, 1137-1144 doi:10.3324/haematol.12838
Copyright © 2008 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van Pel, M.
Right arrow Articles by Fibbe, W. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Pel, M.
Right arrow Articles by Fibbe, W. E.

Hematopoiesis

CD97 is differentially expressed on murine hematopoietic stem-and progenitor-cells

Melissa van Pel1, Henny Hagoort1, Jörg Hamann2, Willem E. Fibbe1

1 Department of Immunohematology and Bloodtransfusion Leiden University Medical Center, Leiden
2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence: Melisssa van Pel, PhD, Section of Stem Cell Biology Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands E-mail:m.van_pel{at}lumc.nl

Background: CD97 is a member of the epidermal growth factor-seven transmembrane (EGF-TM7) family of adhesion receptors and is broadly expressed on hematopoietic cells. The aim of this study was to investigate the expression of CD97 on hematopoietic stem- and progenitor cells (HSC/HPC).

Design and Methods: CD97 expression on hematopoietic stem- and progenitor cells was studied in BALB/c, C57BL/6 and DBA/1 mice using flow cytometry. Functional hematopoietic stem- and progenitor cell characteristics were investigated in vitro and in vivo by progenitor cell assays, cobblestone area forming cell assays and bone marrow cell transplantation.

Results: Analysis of CD97 expression on murine bone marrow cells showed three major populations i.e. CD97HI, CD97INT and CD97NEG cells. Functional studies revealed that radioprotective capacity and cobblestone area forming cell day 28–35 activity resides in the CD97INT bone marrow cell fraction while CFU-GM colony-forming capacity mainly resides in the CD97NEG population in all strains. In C57BL/6 and DBA/1 mice CD97NEG and CD97HI bone marrow cells show hematopoietic stem cell characteristics as well. Further functional analysis of BALB/c CD97INT bone marrow cells revealed that c-KitHICD97INT bone marrow cells exhibit HSC activity and are 1.5-fold enriched for cobblestone area forming cell-day 35 activity compared to c-KitHI bone marrow cells. Moreover, phenotypical analysis showed that BALB/c and C57BL/6 HSC are CD97INT, while DBA/1 HSC are CD97HI.

Conclusions: CD97 is differentially expressed on hematopoietic stem cells and hematopoietic progenitor cells. Committed progenitor cell activity is largely comprised in the CD97NEG fraction, while the CD97INT population contains hematopoietic stem cell activity. In BALB/c mice, CD97 expression can be applied to almost completely separate colony-forming cells and cells exhibiting radioprotective capacity. In addition we propose that the CD97INTc-KitHI phenotype allows simple and rapid purification of murine hematopoietic stem cells.

Key words: hematopoietic stem cells, CD97, mouse model, hematopoietic progenitor cells.