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Exploring the sex and gender differences in the human brain at single cell level

Zelco, Aura (2023) BINP52 20222
Degree Projects in Bioinformatics
Popular Abstract
Exploring the sex and gender differences in the human brain

Sex and gender differences in human brain are both of scientific and societal interest, and impact a wide range of physiological processes, including brain development, behaviour, and disease risk. Currently, sex is defined as biological attributes due to the presence in the person’s genome of XX or XY chromosomes, while the gender identity of a person is composed of the individual’s social roles, behaviours, and expressions. The two have been used interchangeably in clinical studies, and both can affect disease prevalence, progression, treatment, etc.

Although several neurological disorders have different symptoms, prevalence, progression and response to treatment across... (More)
Exploring the sex and gender differences in the human brain

Sex and gender differences in human brain are both of scientific and societal interest, and impact a wide range of physiological processes, including brain development, behaviour, and disease risk. Currently, sex is defined as biological attributes due to the presence in the person’s genome of XX or XY chromosomes, while the gender identity of a person is composed of the individual’s social roles, behaviours, and expressions. The two have been used interchangeably in clinical studies, and both can affect disease prevalence, progression, treatment, etc.

Although several neurological disorders have different symptoms, prevalence, progression and response to treatment across sexes/genders, the possible causes of such differences still elude scientists. The few studies that do explore sex/gender differences, tend to focus on a specific pathology and/or cell population, without considering that age and brain development stages are important factors in differences among sexes/genders.

In this project, we set out to explore sex/gender differences in brain expression. We divided samples based on the sex and age range (from the second trimester of gestation until late adulthood). We also included data from Alzheimer’s disease and multiple sclerosis to compare sex/gender differences in healthy individuals and patients. We used publicly available data from single-nucleus RNA-sequencing (snRNA-seq). RNA carries the information on which genes and how much of the corresponding proteins to build. These proteins shape the activity of a cell, tissue, organ and ultimately body. With snRNA-seq, scientists are able to get a snapshot of the tissue/organ of interest at a single cell level, a level of detail not possible with other techniques and understand the changes different cell populations go through.

We found that cell populations from all ages and disease statuses had different gene expression between sexes, and most sex and gender differentially expressed genes (SG DEGs) were not present on the sex chromosomes. SG DEGs showed little overlap across the developmental stages. Nevertheless, there was extensive overlap in the functional processes the genes were involved in for both sexes. Females showed increased expression of brain-related functions, while males had increased metabolic functions. We also found that hormones, rather than genes directly linked to the sex chromosomes, likely influenced differently the expression in the sexes. Testosterone could indirectly affect greatly the expression of the biased genes in both sexes. Thymosin might influence gene expression in a variety of cell populations predominantly in males. Therefore, these hormones could be one of the probable causes of differential gene expression between the sexes, which might explain differences in drug efficacy and outcome in patients affected by neurological diseases.

We believe that the deep characterization of sex and gender differences performed in this study can help other researchers explain differences in brain behaviours, development and disease risk, and ultimately improve patient care and outcomes of neurological diseases.

Master’s Degree Project in Bioinformatics 60 credits 2023
Department of Biology, Lund University

Advisor: Anagha M. Joshi-Michoel
Computational Biology Unit, University of Bergen, Norway (Less)
Please use this url to cite or link to this publication:
author
Zelco, Aura
supervisor
organization
course
BINP52 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9114269
date added to LUP
2023-05-10 14:46:27
date last changed
2023-05-10 14:46:27
@misc{9114269,
  author       = {{Zelco, Aura}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Exploring the sex and gender differences in the human brain at single cell level}},
  year         = {{2023}},
}