TY - JOUR
T1 - In vivo expansion of the megakaryocyte progenitor cell population in adult CD26-deficient mice
AU - Kidd, Shannon
AU - Bueso-Ramos, Carlos
AU - Jagan, Sucheta
AU - Paganessi, Laura A.
AU - Boggio, Lisa N.
AU - Fung, Henry C.
AU - Gregory, Stephanie A.
AU - Christopherson, Kent W.
N1 - Funding Information:
We thank John Crispino (Feinberg School of Medicine at Northwestern University, Chicago, IL) for technical assistance and generously providing us with a working immunohistochemistry protocol for the VWF antibody. We also thank Elizabeth A. Paganessi and Lydia Luy Tan for their technical assistance. This work was supported primarily by the National Blood Foundation (Bethesda, MD, USA)/American Association of Blood Banks (Bethesda, MD, USA) through a research grant to K.W.C (031824). K.W.C. was also supported during this research period by grants from the American Association for Cancer Research (Philadelphia, PA, USA) ( 07-10-19-CHRI ), Leukemia & Lymphoma Society (White Plains, NY, USA) ( 6044-08 ), and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (Bethesda, MD, USA) (DK074892) , Rush Translational Science Consortium (Chicago, IL, USA), and Rubschlager Foundation (Chicago, IL, USA). S.M.K. was supported by fellowships granted by the American Legion Auxiliary in Texas (Austin, TX, USA) and the Rosalie B. Hite Foundation.
PY - 2011/5
Y1 - 2011/5
N2 - Objective: Megakaryopoiesis involves commitment of hematopoietic stem cells (HSC) toward the myeloid lineage in combination with the proliferation, maturation, and terminal differentiation of progenitors into megakaryocytes. The exact mechanism of megakaryocyte development from HSC is unknown, but growth factors such as thrombopoietin have been identified as critical. Additionally, it has been suggested that the chemokine CXCL12/stromal-cell derived factor-1α has a role in regulating megakaryopoiesis and thrombopoiesis. We recently reported the importance of the extracellular protease CD26 (dipeptidylpeptidase IV) in regulating HSC responses to CXCL12, as well as modulating HSC trafficking into and out of the bone marrow. However, the importance of CD26 for megakaryopoiesis has not been reported. We therefore compared megakaryocyte development between CD26-deficient (CD26/) mice and C57BL/6 control mice. Materials and Methods: Adult CD26 mice and C57BL/6 control mice were evaluated using blood differentials, histological analysis, flow cytometric analysis, and progenitor colony assays. Results: Bone marrow from CD26 mice has a significantly expanded megakaryocyte and megakaryocyte progenitor population compared to control C57BL/6 mice bone marrow. Conclusions: Our results indicate that endogenous CD26 normally suppresses megakaryopoiesis and that loss of CD26 activity results in expansion of the megakaryocyte progenitor population in vivo. This suggests the potential use of CD26 inhibitors to improve megakaryocyte progenitor function and/or reconstitution of the megakaryocyte cell population.
AB - Objective: Megakaryopoiesis involves commitment of hematopoietic stem cells (HSC) toward the myeloid lineage in combination with the proliferation, maturation, and terminal differentiation of progenitors into megakaryocytes. The exact mechanism of megakaryocyte development from HSC is unknown, but growth factors such as thrombopoietin have been identified as critical. Additionally, it has been suggested that the chemokine CXCL12/stromal-cell derived factor-1α has a role in regulating megakaryopoiesis and thrombopoiesis. We recently reported the importance of the extracellular protease CD26 (dipeptidylpeptidase IV) in regulating HSC responses to CXCL12, as well as modulating HSC trafficking into and out of the bone marrow. However, the importance of CD26 for megakaryopoiesis has not been reported. We therefore compared megakaryocyte development between CD26-deficient (CD26/) mice and C57BL/6 control mice. Materials and Methods: Adult CD26 mice and C57BL/6 control mice were evaluated using blood differentials, histological analysis, flow cytometric analysis, and progenitor colony assays. Results: Bone marrow from CD26 mice has a significantly expanded megakaryocyte and megakaryocyte progenitor population compared to control C57BL/6 mice bone marrow. Conclusions: Our results indicate that endogenous CD26 normally suppresses megakaryopoiesis and that loss of CD26 activity results in expansion of the megakaryocyte progenitor population in vivo. This suggests the potential use of CD26 inhibitors to improve megakaryocyte progenitor function and/or reconstitution of the megakaryocyte cell population.
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U2 - 10.1016/j.exphem.2011.01.012
DO - 10.1016/j.exphem.2011.01.012
M3 - Article
C2 - 21291952
AN - SCOPUS:79955149047
SN - 0301-472X
VL - 39
SP - 580-590.e1
JO - Experimental Hematology
JF - Experimental Hematology
IS - 5
ER -