EVALUATION OF THE MECHANISM BY WHICH T CELLS CONTRIBUTE TO THE EXPANSION OF HSCS INDUCED BY OVX.

• Grant number: 14/27231-5
• Support Opportunities: Scholarships abroad - Research
• Start date: July 15, 2015
• End date: July 14, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Marcelo Luis Steiner
• Grantee: Marcelo Luis Steiner
• Host Investigator: Roberto Pacifici
• Host Institution: Faculdade de Medicina do ABC (FMABC). Santo André , SP, Brazil
• Institution abroad: Emory University, United States

Abstract

There are some evidences that a model of acute estrogen (E) deprivation, expands the Hematopoietic Stem Cell (HSC) population of the bone marrow (BM) through T cells. Aiming to prove and to broad these matter this project were developed. Female WT C57BL/6 mice and several congenic KO mice strains paired to the proper age matched control littermates will be used. All mice are going to performing ovx or shaw operation. They will be left untreated or will be estradiol replaced. Production/expression of sIL-6R, Wnt10b and CD40L of bone marrow and spleen CD4+ and CD8+T and the expression of IL-6 and of the Notch ligands Jagged 1 and d-like-1 by BM stem cells (SCs)cells will be measured. BM will also be utilized to measure the relative and absolute number of HSC subsets based on differential expression of 'signalling lymphocyte activation molecule' (SLAM) receptors. In addition we will measure the level of the Notch1 intracellular domain (NICD), HSC apoptosis, the expression of the Notch downstream genes Hes-1 and Deltex-1 and we will prepare longitudinal sections of decalcified femurs and measure Jagged 1 and d-like-1 expression in osteoblasts (OBs). All data collected from the different models will be compared and analyzed.