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An In Vitro Study on the Role of Endothelial Cell Connexin43 Gap Junctions in the Regulation of Hematopoietic Stem and Progenitor Cells Traffic
Pirman, Megan

2010, MS, University of Cincinnati, Allied Health Sciences : Transfusion and Transplantation Medicine.

Cell-to-cell contact between hematopoietic stem cells and progenitors (HSC/P) and their supporting bone marrow (BM) microenvironment has been shown to be pivotal in blood formation and hematopoietic homeostasis between BM and peripheral blood. BM derived endothelial cells (EC) form a major cell component in the hematopoietic microenvironment. BMEC are fenestrated to allow the traffic of hematopoietic cells to and from the circulation while maintaining adhesion and communication with other EC and HSC/P. Gap junctions (GJ) represent one system in which adjacent cells adhere in order to communicate intercellularly. GJ are channels constituted by a group of proteins called connexins (Cx). It is known that Cx43 GJ are involved in the interactions between hematopoietic cells and the BM microenvironment. Based on in vivo preliminary data indicating loss of retention of HSC/P in BM of endothelial-specific Cx43-deficient mice, we hypothesized that the loss of Cx43 would induce a decreased adhesion and/or increased migration of HSC/P, respectively, to or through Cx43-deficient EC.

Our results indicate that the deficiency of Cx43 in EC, induced by RNA interference induces decreased adhesion and increased transendothelial migration of normal HSC/P. However, the transendothelial migration of Cx43-deficient HSC/P through Cx43 RNA-silenced EC is not modified, suggesting that the mechanisms mediated by Cx43 involved in the control of transendothelial migration are more complex than anticipated. In summary, Cx43 deficiency in the EC compartment may induce a complex array of changes in the proliferation, adhesion and migration of HSC/P. Migration of HSC/P, however, seems to depend on the expression of Cx43 in both EC and HSC/P. Cx43 plays pleiotropic, cell-specific roles in the hematopoietic microenvironment.


Jose Cancelas-Perez, MD (Committee Chair)
Thomas Leemhuis, PhD (Committee Member)
Susan Wilkinson, EdD (Committee Member)
73 p.

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Pirman, M. (2010). An In Vitro Study on the Role of Endothelial Cell Connexin43 Gap Junctions in the Regulation of Hematopoietic Stem and Progenitor Cells Traffic. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Pirman, Megan. "An In Vitro Study on the Role of Endothelial Cell Connexin43 Gap Junctions in the Regulation of Hematopoietic Stem and Progenitor Cells Traffic." Electronic Thesis or Dissertation. University of Cincinnati, 2010. OhioLINK Electronic Theses and Dissertations Center. 05 Jul 2015.

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Pirman, Megan "An In Vitro Study on the Role of Endothelial Cell Connexin43 Gap Junctions in the Regulation of Hematopoietic Stem and Progenitor Cells Traffic." Electronic Thesis or Dissertation. University of Cincinnati, 2010. https://etd.ohiolink.edu/

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