Abstract
Hematopoiesis is the process in which cells of lymphatic and hematopoietic systems are produced starting from the precursors that have multipotency and self renewal capabilities - the hematopoietic stem cells (HSC). To a proper mature progeny maintenance and production, there are many involved mechanisms, mainly in issues of HSC proliferation and differentiation, in which most of them are modulated by cytokines. Besides cytokines and receptors diversity, an ubiquitous ion calcium (Ca2+) signaling can be observed. Intracellular Ca2+ is the most versatile second messenger, taking part in several processes, as proliferation, differentiation, cell death, contraction, secretion, and even fecundation and learning. Our group has shown that HSC stimulated with cytokines (IL-3, GM-CSF, G-CSF, M-CSF, SCF, IL-6, IL-7) presents small and oscillatory cytosolic variations of Ca2+ concentrations, what seems to be related to proliferation and differentiation processes. It is unknown which Ca2+ signaling mechanism modulate hematopoiesis however, time, intensity and location of these Ca2+variations seems to have roles in intracellular pathways that regulate hematopoiesis. In several pathologies, such as leukemia, the cellular control mechanism of proliferation and differentiation (related to Ca2+ signaling) may be altered. The aim of this project is to investigate Ca2+ signals generated by cytokines (IL-3 and GM-CSF), considering time, intensity and location, and correlate the generated Ca2+ signals with proteins and intracellular pathways triggered, in normal and leukemic HSC. This study will provide a better understanding of HSC regulation and its relation with hematologic cancers.
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