Identification of long non-coding RNAs involved in the cell development regulation program of human trophoblasts

• Grant number: 21/06005-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2021
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Thalles Souza Lopes
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes, AP.TEM

Abstract

The placenta is responsible for modulating intrauterine interactions, for actively maintaining the homeostasis of this environment, in addition to acting as an important immunological mediator. However, the molecular mechanisms by which viral agents reach the fetal compartment are not clearly understood. Given this scenario, a study of differential gene expression conducted in 2020 by our group, evaluated the natural susceptibility of placental trophoblasts, cells that act as a natural barrier to Zika Virus (ZIKV), induced in vitro from induced Pluripotent Stem Cells (iPSCs) from three pairs of dizygotic and discordant twins for the congenital ZIKV Syndrome (CSZ). This study showed a differential expression of genes encoding proteins expressed in trophoblasts among these individuals. Nevertheless, the involvement of lncRNAs in the cellular development of trophoblasts and in the susceptibility of the placenta to ZIKV has not been evaluated. A wealth of scientific evidence has revealed that regulation of cell development and stem cell differentiation into other specialized cell types is orchestrated in part by lncRNAs. Still, the role of these agents in the cell development regulation program of human trophoblasts remains poorly explored in the literature. Thus, this project aims to evaluate the role of lncRNAs in this process, in the absence and presence of ZIKV infection, using differential expression analysis and RNA-Seq data. The generated data will allow to describe a set of lncRNAs involved in the regulation of cell development of human trophoblasts, and to identify possible lncRNAs involved in placental susceptibility to ZIKV in the context of exposure to the virus during pregnancy. (AU)