Molecular mechanisms of megakaryopoiesis

Abstract

One function of bone marrow megakaryocytes (MKs) is the controlled release of platelets into the circulation. Over the past few years, molecular mechanisms that contribute to MK development and differentiation have begun to be elucidated. This review provides a brief overview of megakaryopoiesis and platelet function, and the importance of selected hematopoietic transcription factors (including GATA-1, FOG, Fli-1, AML1, and NF-E2) and target genes in this biological process. In addition, a discussion of human diseases affecting megakaryopoiesis and mouse models of thrombocytopenia are presented with emphasis on how these systems have and will continue to provide further insights into mechanisms that control the biological functions of the megakaryocytic cell lineage. Ultimately, such knowledge may provide the basis for novel therapeutic approaches for modulation of platelet number and function.

CDC6 expression is regulated by lineage-specific transcription factor GATA1

“…In fact, transcriptional control of most of these lineages genes has been shown to depend on GATA1 activity. 15,21,22,39,40 However, final differentiation and maturation of these cells is accompanied by changes in cell proliferation and therefore in cell cycle status: megakaryocytic maturation is characterized Mutagenesis Kit (Stratagene). The DNA sequence of all mutant and/or tag-fused cDNAs were verified accordingly.…”

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

“…12 Moreover, to our knowledge, there are no reports exploring the possible role of ROS and NADPH oxidases in the differentiation of HSCs or in other haematopoietic lineages other than macrophages, including megakaryocytic differentiation, that is, the process of maturation of megakaryocytes from HSCs that releases circulating platelets. 13 K562 and HEL cells are commonly used to study different aspects related to megakaryocytopoiesis because they undergo megakaryocytic differentiation in response to phorbol esters. 14,15 Accordingly, our goal was to study the putative role of ROS in megakaryocytic differentiation using both cell lines and human CD34 þ cells, to gain insight into the principles that might help in our understanding of how haematopoiesis is regulated and how NADPH oxidase ROS production helps general cell differentiation.…”

Quantitative Trait Loci Analysis for Peripheral Blood Parameters in a (BALB/cW * C57BL/6J-Mpl hlb219/J) F2 Mice

“…The set of genes affecting the level of PLT and other blood cell parameters is also extensive [37]. The mutation in the thrombopoietin receptor gene Mpl (54.61cM) found by Chan et al [6] in HLB219 mice is the reason for the connection between the platelet count in peripheral blood of F 2 mice and the central region of chromosome 4.…”