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TISSUE-SPECIFIC STEM CELLS

Timing and Expression Level of Protein Kinase C Regulate the Megakaryocytic Differentiation of Human CD34 Cells

^aDepartment of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, via Gramsci, Parma, Italy;
^bCellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, Bologna, Italy;
^cIstituto di Genetica Molecolare-Consiglio Nazionale delle Ricerche, Unit of Bologna, c/o Istituti Ortopedici Rizzoli, Bologna, Italy

Key Words. Megakaryocytopoiesis • Stem cells • Cytokines • Thrombopoietin • Tumor necrosis factor-related apoptosis-inducing ligand

Correspondence: Marco Vitale, M.D., Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, Via Gramsci, 14, I-43100 Parma, Italy. Telephone: +39.0521.033032; Fax: +39.0521.033033; e-mail: marco.vitale{at}unipr.it

Received on December 29, 2006; accepted for publication on June 5, 2007.

First published online in STEM CELLS EXPRESS  June 14, 2007.


Protein kinase C (PKC)-mediated intracellular signaling participates in several key steps of hematopoietic cell differentiation. The isoform of PKC has been associated with erythroid differentiation as well as with the early phases of megakaryocytic (MK) lineage commitment. Here, we worked on the hypothesis that PKC expression levels might be modulated during MK differentiation, with a specific role in the early as well as in the late phases of thrombopoiesis. We demonstrate that—at variance with the erythroid lineage development—PKC is completely downmodulated in TPO-induced CD34 cells from day 6 onward. The forced expression of PKC in the late phases of MK differentiation delays the phenotypic differentiation of progenitors likely via Bcl-xL upregulation. Moreover, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), known as a negative regulator of early erythroid expansion, is not apoptogenic for thrombopoietin-induced CD34 cells, but rather accelerates their maturation. However, PKC levels negatively interfere also with the effects of TRAIL in MK differentiation. PKC can therefore be considered a signaling intermediate whose expression levels are finely tuned, with a virtually opposite kinetic, in erythroid versus megakaryocytic lineages, to adequately respond to the signaling requirements of the specific hematopoietic lineage.

Disclosure of potential conflicts of interest is found at the end of this article.

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