Investigation of molecular mechanisms associated with sexual dimorphism in humans

Author(s)

Amanda Pereira Vasconcelos

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2024-08-27

Examining board members

Helder Takashi Imoto Nakaya; João Marcelo Pereira Alves; Ana Tereza Ribeiro de Vasconcelos

• Advisor: Helder Takashi Imoto Nakaya

Abstract

Sexual dimorphism is widely observed in various clinical conditions as well as in healthy individuals, significantly impacting human health. This work addresses transcriptome analyses to investigate molecular signatures involving sexual differences in humans. First, we investigated sexual dimorphism in healthy human cells and tissues using data from the Genotype-Tissue Expression (GTEx) project and single-cell data. Additionally, we introduced the XYAnalyzer, a tool for annotating sample sex based on gene expression. This study elucidated various differentially induced genes in both sexes and demonstrated significant tissue-specific differences. Several signatures associated with B lymphocytes and antibody-secreting B cells were found in the thyroid of women, potentially explaining the predisposition to autoimmune diseases in females. Second, we analyzed sexual differences in the context of sepsis. For this, we selected sepsis studies and conducted various transcriptome analyses. We identified consistent gene signatures between men and women, highlighting the presence of several immune system markers. Furthermore, a high density of co-expressed genes, as well as enriched signaling pathways, were identified in prepubertal individuals. Finally, we found different proportions of cell types in men and women, such as neutrophils and monocytes. However, prepubertal girls exhibited decreased CD8 T lymphocytes and differentially expressed canonical markers of these cells. The results presented in this work elucidate various transcriptional-level molecular differences between men and women in both healthy conditions and sepsis. (AU)

• FAPESP's process: 19/27146-1 - Integration of transcriptome data with clinical and immunological data
• Grantee: Amanda Pereira Vasconcelos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)