Am J Blood Res 2012;2(4):228-242
Original Article
Growth factor independence 1 (Gfi1) regulates cell-fate decision of a
bipotential granulocytic-monocytic precursor defined by expression of Gfi1
and CD48
Lothar Vassen, Ulrich Dührsen, Christian Kosan*, Hui Zeng, Tarik Möröy
Institut de recherches cliniques de Montréal IRCM, Montreal, QC, Canada; Westdeutsches Tumorzentrum Klinik
für Hämatologie Universitätsklinikum Essen Hufelandstrasse 55 45122 Essen, Germany; Institute of Infectious
Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Département de Microbiologie et Immunologie,
Université de Montréal, Montréal, QC, H2W1R7 Canada. *present address: Center for Molecular Biomedicine
(CMB), Department of Biochemistry, Friedrich-Schiller-University Jena, Hans-Knöll-Str. 2, D-07745 Jena.
Received October 31, 2012; Accepted November 15, 2012; Epub November 25, 2012; Published November 30, 2012
Abstract: The transcriptional repressor Gfi1 regulates the expression of genes important for survival, proliferation and
differentiation of hematopoietic cells. Gfi1 deficient mice are severely neutropenic and accumulate ill-defined CD11b+GR1int
myeloid cells. Here we show that Gfi1 expression levels determine mono- or granulocytic lineage choice in precursor cells. In
addition, we identify CD48 as a cell surface marker which enables a better definition of monocytes and granulocytes in mouse
bone marrow. Using the CD48/Gr1/Gfi1 marker combination we can show that the CD11b+Gr1int cells accumulating in Gfi1
deficient mice are monocytes and not granulocyte precursors. Expression of CD48, Gr1 and Gfi1 define different bone marrow
subpopulations that are either committed to the granulocytic lineage, or bipotential precursors of granulocytes or monocytes.
Finally, a comparison of genes differentially expressed between murine Gfi1 high granulocytic precursors and mature
granulocytes with gene expression changes from human myeloblasts versus neutrophils show a strong resemblance of
human and mouse differentiation pathways. This underlines the value of the markers CD48 and Gfi1 identified here to study
human and murine granulo-monocytic differentiation.(AJBR1210006).
Keywords: Gfi1, CD48, CD106, granulocyte, monocyte, myelopoiesis, neutropenia
Address all correspondence to:
Dr. Tarik Möröy
Institut de recherches cliniques de Montréal (IRCM)
110 des Pins West Avenue,
Montréal, Québec, H2W 1R7, Canada.
Tel: 1 (514) 9875501; Fax: 1 (514)
9875679; E-mail: Tarik.Moroy@ircm.qc.ca;
Or: Dr. Hui Zeng, Institute of Infectious Diseases
Beijing Ditan Hospital, Capital Medical University
Beijing, China.
E-mail: zenghui@ccmu.edu.cn
Original Article
Growth factor independence 1 (Gfi1) regulates cell-fate decision of a
bipotential granulocytic-monocytic precursor defined by expression of Gfi1
and CD48
Lothar Vassen, Ulrich Dührsen, Christian Kosan*, Hui Zeng, Tarik Möröy
Institut de recherches cliniques de Montréal IRCM, Montreal, QC, Canada; Westdeutsches Tumorzentrum Klinik
für Hämatologie Universitätsklinikum Essen Hufelandstrasse 55 45122 Essen, Germany; Institute of Infectious
Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Département de Microbiologie et Immunologie,
Université de Montréal, Montréal, QC, H2W1R7 Canada. *present address: Center for Molecular Biomedicine
(CMB), Department of Biochemistry, Friedrich-Schiller-University Jena, Hans-Knöll-Str. 2, D-07745 Jena.
Received October 31, 2012; Accepted November 15, 2012; Epub November 25, 2012; Published November 30, 2012
Abstract: The transcriptional repressor Gfi1 regulates the expression of genes important for survival, proliferation and
differentiation of hematopoietic cells. Gfi1 deficient mice are severely neutropenic and accumulate ill-defined CD11b+GR1int
myeloid cells. Here we show that Gfi1 expression levels determine mono- or granulocytic lineage choice in precursor cells. In
addition, we identify CD48 as a cell surface marker which enables a better definition of monocytes and granulocytes in mouse
bone marrow. Using the CD48/Gr1/Gfi1 marker combination we can show that the CD11b+Gr1int cells accumulating in Gfi1
deficient mice are monocytes and not granulocyte precursors. Expression of CD48, Gr1 and Gfi1 define different bone marrow
subpopulations that are either committed to the granulocytic lineage, or bipotential precursors of granulocytes or monocytes.
Finally, a comparison of genes differentially expressed between murine Gfi1 high granulocytic precursors and mature
granulocytes with gene expression changes from human myeloblasts versus neutrophils show a strong resemblance of
human and mouse differentiation pathways. This underlines the value of the markers CD48 and Gfi1 identified here to study
human and murine granulo-monocytic differentiation.(AJBR1210006).
Keywords: Gfi1, CD48, CD106, granulocyte, monocyte, myelopoiesis, neutropenia
Address all correspondence to:
Dr. Tarik Möröy
Institut de recherches cliniques de Montréal (IRCM)
110 des Pins West Avenue,
Montréal, Québec, H2W 1R7, Canada.
Tel: 1 (514) 9875501; Fax: 1 (514)
9875679; E-mail: Tarik.Moroy@ircm.qc.ca;
Or: Dr. Hui Zeng, Institute of Infectious Diseases
Beijing Ditan Hospital, Capital Medical University
Beijing, China.
E-mail: zenghui@ccmu.edu.cn
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