The commitment of the totipotent hematopoietic stem cell into the different progenitors of the blood cells is a key event in the production of the needed number of each cell type. This process is tightly regulated by a number of factors (cytokines, interleukins and colony stimulating factors) and their receptors (1). In response to these external stimulations, categories of genes are turned on or off, establishing progressively a specific pattern of gene expression, representing the transcriptional status of a specific lineage at a given differentiation stage. The transcription of these genes is controlled by a network of transcription factors that associate lineage specific and ubiquitous factors (2). Studies of the regulatory elements found in the promoters and enhancers of erythroid and megakaryocytic genes have revealed striking homologies, indicating that the mechanisms controlling gene expression in these two lineages are probably very similar. For example, the zinc finger transcription factor GATA1, which was originally described as an erythroid specific factor (3, 4) is in fact also expressed in megakaryocytes and mastcells (5, 6). In addition, this factor regulates the transcription of megakaryocyte specific genes (7). This observation is consistent with the hypothesis suggesting that these two lineages may arise from a common precursor. Nevertheless, several genes, like the gene encoding platelet glycoprotein lib (GPIIb), are only expressed in the megakaryocytes, and some others like the globin genes are only expressed in erythroid cells. In this study, we propose a mechanism that could explain the megakaryocyte specific expression of GPIIb gene.

We describe a cellular model based on the hematopoietic differentiation of embryonic stem (ES) cells. We demonstrate that under defined culture conditions, this system allows the production of megakaryocytes, at differentiation stages ranging from immature progenitors to mature megakaryocytes. This system is very useful to monitor the regulation of the GPIIb gene in the course of megakaryocytic differentiation.