Transcriptome analysis of platelet-activating factor (PAF) receptor regulatory networks during retinal stem cells neurophysiological maturation

• Grant number: 22/14826-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): March 27, 2023
• Effective date (End): March 26, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Carolina Beltrame Del Debbio
• Grantee: Bárbara Dalmaso
• Supervisor: Claudia Pommerenke
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Germany
• Associated to the scholarship: 20/11352-9 - The role of PAF receptor in retinal stem cell reprogramming and differentiation, BP.DD

Abstract

The retina is a Central Nervous System tissue essential for the visual information processing. Due to structural, biochemistry and functional complexity of the retina, the developmental regulatory mechanisms and maturation cues are highly controlled during retinogenesis. It is essential to understand the mechanisms that regulate the maintenance of mammalian retinal stem cells and the mechanisms involved in cell differentiation. In our lab, we are studying the roles of the Platelet Activating Factor Receptor (PAFR) in retinal stem cells maintenance and differentiation. PAF is an important mediator of cell proliferation, including neuroblasts regulation during retinal development. Our results indicated that PAFR is less expressed in retinas under development than differentiated retinas. The inhibition of PAFR activity is important for retinal progenitor cells maintenance, as we observed that PAFR knockout animals (PAFR-/-) presented higher transcriptional rates of proliferation and progenitor markers than controls. During retinal differentiation, the presence of PAFR is important to regulate the expression of neural differentiation transcripts (Map2 and Tubb3) as well as mature neuronal markers, as photoreceptors. Adult PAFR knockout animals expressed lower rates of neuronal differentiated marker that reflected in the functional activity of the retina. PAFR depleted animals presented altered electroretinogram (ERG) results indicating altered retinal neural function. Here we propose to analyze the transcriptional profile of the PAFR-/- animals by RNA sequencing and bioinformatic analysis and compare to wild type mice. These results will help to understand the role of PAFR signaling and downstream regulators in retinal neurogenesis and synaptogenesis. (AU)