title: In vivo expansion of the megakaryocyte progenitor cell population in adult CD26-deficient mice.
abstract: 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.
  
  
  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.
authors.affiliation: The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Kidd
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Sucheta
authors.initials: S
authors.lastname: Jagan
authors.forename: Laura A
authors.initials: LA
authors.lastname: Paganessi
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Boggio
authors.forename: Henry C
authors.initials: HC
authors.lastname: Fung
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
authors.forename: Kent W
authors.initials: KW
authors.lastname: Christopherson
mesh_terms: D000818:Animals; D002455:Cell Division; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency* / Q000378:metabolism; D005434:Flow Cytometry; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015999:Multivariate Analysis
chemical_list: D018819:Dipeptidyl Peptidase 4