Multispecies single-cell transcriptomic atlas of the hypothalamus: tracking the evolutive pathways taken by the peptidergic neurons

• Grant number: 24/14265-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: December 01, 2024
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Andre de Souza Mecawi
• Grantee: Victor Jardim Duque
• Supervisor: Irene Papatheodorou
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Earlham Institute, England
• Associated to the scholarship: 21/14426-6 - Multiomic analysis (RNAseq and ATACseq) in single-cell nuclei of the hypothalamus of normal mice and during pre-eclamptic gestation, BP.DD

Abstract

The peptidergic neurons located in the hypothalamus are essential for the survival of vertebrate species, playing an essential role in the regulation of multiple homeostatic functions and behaviors. Those neurons produce and realize several neuropeptides that can work as hormones or neurotransmitters, such as vasopressin, oxytocin, pro-opiomelanocortin, agouti-related protein, and neuropeptide Y, among others. With the advancement of single-cell sequencing technology (scRNA-Seq), it is now possible to identify the transcriptome signature of specific cells, allowing us to understand the regulatory roles of specific genes in specific cells from any target tissues and organs. Given its relevance, various single-cell atlases have been developed in the literature with the goal of integrating scRNA-Seq data to increase the number of cells and improve the statistical power and analytical options, such as interspecies comparison. Interspecies comparison holds huge potential for revealing transcriptional divergences related to species evolution, especially for cells critical to many species' survival, such as hypothalamic peptidergic neurons. Thus, developing a multi-species hypothalamic atlas has the potential to help identify species with transcriptomically similar cell types, indicating the most effective vertebrate species to use as animals' models for understanding the physiology and pathological processes related to the hypothalamic peptidergic neurons. Furthermore, it will allow the understanding of genetic and transcriptomic conservation and divergences among the hypothalamic peptidergic neurons involved in vertebrate species' evolutionary processes. Finally, using the newly created interspecies atlas of hypothalamic peptidergic neurons along with scRNA-Seq data from invertebrate peptidergic neurons, we will have the opportunity to uncover the molecular and cellular evolutionary origins of the vertebrate hypothalamic neuronal diversity. This understanding has the potential to improve the efficiency with which findings achieved using experimental animal models to investigate neuropeptidergic-related physiological and pathophysiological processes, such as metabolic, hypertensive, reproductive, and psychiatric disorders, can be translated into clinical applications.