sex and gender differences in the human brain at transcription level during development and disease

Anagha Joshi

Professor (University of Bergen), visiting professor (IIT Madras)

Sex and gender (SG) differences in the human brain are of interest to society and science as numerous processes are impacted by them, including brain development, behavior, and diseases. I will first provide a quick overview of the sex and gender differences in human brain and then further highlight two published works to systematically identify and characterize SG-biased genes by collecting publicly available single-cell data from the in-utero to elderly age in healthy, Alzheimer’s disease and multiple sclerosis sample. Sex and gender differences in the transcriptome were present through- out the lifespan and across all cell types. Although there was limited overlap among SG-biased genes across different age and disease groups, we observed significant functional overlap. Female-biased genes are consistently enriched for brain-related processes, while male-biased genes are enriched for metabolic path- ways. Additionally, mitochondrial genes showed a consistent female bias across cell types. We also found that androgen response elements (not estrogen) were significantly enriched in both male- and female-biased genes, and thymosin hormone targets being consistently enriched only in male-biased genes. The significant enrichment of androgen (not estrogen) response elements in both male- and female-biased genes suggests that androgens are important regulators likely establishing these SG differences in both males and females.