Role of P2X7 purinergic receptor in the regulation of hematopoietic stem cell and myeloid lineage

Abstract

The importance of the hematopoietic stem cell (HSC) lies in its potential to repopulate the bone marrow forming all cell types of the lymphohematopoietic system being the main focus of the study. Thus, the knowledge of the mechanisms that control the HSC and molecules that allow its manipulation has an enormous scientific and clinical importance. Our group has investigated the intracellular pathways that control the HSC, and the crosstalk among intracellular pathways, identifying mechanisms of self-renewal and differentiation, using cytokines (IL-3, GM-CSF, G-CSF, M-CSF, SCF) and purinergic receptors (sensitive to ATP and analogs) as hematopoietic activators. Additionally, we have found negative modulators of HSC, such as ATP and nitric oxide, whose antitumoral potential against leukemic stem cells is under investigation. In this project, our goal is to further study the role of purinergic receptors in the modulation of HSC and in myeloid differentiation investigating mainly the function of the P2X7 receptor in a mouse model P2X7fl/fl, recently acquired. The P2X7 receptor is a ligand-gated cation channel and its activation leads to the formation of a membrane pore that allows molecules up to 900 Da. The activity of the P2X7 receptor is mainly associated with the immune system; however, there are few studies on primitive hematopoietic cells (HSC and progenitors). The use of this animal model will allow obtaining important information regarding the function of the P2X7 receptors in murine hematopoiesis: more specifically in the ontogeny of the HSC and in the myeloid differentiation. (AU)