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Subcellular Ca2+ signaling aspects in proliferation control of haemopoietic stem cells by interleukin-3 and granulocyte/macrophage colony stimulating factor

Grant number: 15/24464-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2016
Effective date (End): November 11, 2018
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Edgar Julian Paredes-Gamero
Grantee:Marina Mastelaro de Rezende
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil
Associated scholarship(s):16/23787-4 - Wnt and Ca2+ signaling in normal and leukemic hematopoietic stem cell fate, BE.EP.DR


Hematopoiesis is the process in which cells of lymphatic and hematopoieticsystems are produced starting from the precursors that have multipotency and selfrenewalcapabilities - the hematopoietic stem cells (HSC). To a proper mature progenymaintenance and production, there are many involved mechanisms, mainly in issues ofHSC proliferation and differentiation, in which most of them are modulated bycytokines. 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 stimulatedwith cytokines (IL-3, GM-CSF, G-CSF, M-CSF, SCF, IL-6, IL-7) presents small andoscillatory cytosolic variations of Ca2+ concentrations, what seems to be related toproliferation and differentiation processes. It is unknown which Ca2+ signalingmechanism modulate hematopoiesis however, time, intensity and location of these Ca2+variations seems to have roles in intracellular pathways that regulate hematopoiesis. Inseveral pathologies, such as leukemia, the cellular control mechanism of proliferationand differentiation (related to Ca2+ signaling) may be altered. The aim of this project isto investigate Ca2+ signals generated by cytokines (IL-3 and GM-CSF), consideringtime, intensity and location, and correlate the generated Ca2+ signals with proteins andintracellular pathways triggered, in normal and leukemic HSC. This study will provide abetter understanding of HSC regulation and its relation with hematologic cancers.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE REZENDE, MARINA MASTELARO; NG-BLICHFELDT, JOHN-POUL; JUSTO, GISELLE ZENKER; PAREDES-GAMERO, EDGAR JULIAN; GOSENS, REINOUD. Divergent effects of Wnt5b on IL-3-and GM-CSF-induced myeloid differentiation. CELLULAR SIGNALLING, v. 67, MAR 2020. Web of Science Citations: 0.
DE REZENDE, MARINA MASTELARO; FERREIRA, ALICE T.; PAREDES-GAMERO, EDGAR J. Leukemia stem cell immunophenotyping tool for diagnostic, prognosis, and therapeutics. Journal of Cellular Physiology, NOV 2019. Web of Science Citations: 0.

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