The functions of Ikaros in differentiation of B-1 cells in phagocytes in vitro

• Grant number: 13/22219-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2013
• End date: November 30, 2014
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Ana Flavia Popi
• Grantee: Ana Clara Pires Sodré
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/50256-6 - B-1 cells: biology, relations with other cells of the immune system and participation in different experimental models, AP.TEM

Abstract

The hematopoietic system is continuously regenerated by a rare population of multipotent stem cells and self-renewable, resident in adult bone marrow. Transcription factors regulate gene expression by inducing or silencing of specific genes, which leads to a cell commitment to a lineage defined. In the hierarchical model, hematopoietic stem cells ramify primarily among lymphoid and myeloid progenitors. Our group has shown that B-1 cells expressing both transcription factors restricted so as myeloid lymphoid lineage, thus defying the paradigm of differentiation of hematopoietic cells. Ikaros, Aiolos and Helios encode transcription factors that are important regulators of lymphoid development and differentiation. These proteins are involved in the control of gene expression and when associated with nuclear complexes participate in nucleosomal remodeling. Due to the expression of various isoforms with different functions and links to DNA Ikaros is identified as model for the study of post-transcriptional changes involved in cellular transformation and differentiation of the hematopoietic system. In the absence of Ikaros, hematopoietic progenitors are prevented from developing B and T lymphocytes, they show reduced expression of genes lymphoid cells, such as FLT3, IL7-R and sharp increase in the myeloid lineage. Considering the promiscuous expression of lymphoid and myeloid genes by B-1 cells, this project aims to investigate the role of Ikaros in the differentiation of B-1 cells to phagocytes.