GENE MODULATION OF LET7A/LIN28B AXIS TO EVALUATE DEVELOPMENT, MATURATION AND LONG-TERM SURVIVAL MECHANISMS OF HUMAN FETAL VERSUS HUMAN ADULT B CELLS

• Grant number: 23/16705-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: May 24, 2024
• End date: May 23, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Flavia Popi
• Grantee: Olívia Fonseca Souza
• Supervisor: Eliver Eid Bou Ghosn
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Emory University, United States
• Associated to the scholarship: 19/27009-4 - MicroRNAs and apoptosis evaluation in B-1 cells progenitors along aging, BP.DD

Abstract

B cell development represents a very orchestrated pathway that initiates with hematopoietic stem cells resulting in mature B lymphocytes, which will participate in immunological responses. The genetic program for this lymphopoiesis differs between fetal and adult human samples and is regulated by several molecules, including microRNAs. The axis formed by the microRNA Let7 and its regulator LIN28B is highly expressed in fetal life. It is already described its role in fetal or adult B differentiation and its relation to oncogenic processes based on targets that these molecules present, such as ARID3A, MYC, RAS, and HMGA2. The identification of progenitors found in fetal but not present in adult life, together with distinct molecular pathways represents an interesting approach to understanding malignancies emergence, since fetal B cells are already related to the origin of some leukemias. Based on that, this project aims to evaluate the development, differentiation and survival of fetal or adult human B cells after gene modulation of let7a/Lin28b axis.