Publicação

Characterization of the choroid plexus cells transcriptome during development

Ver documento

Detalhes bibliográficos
Resumo:The choroid Plexus (CP) is a brain tissue responsible for the production and secretion of the cerebrospinal fluid (CSF). It lays at the interface of the peripheral blood and the brain, forming the blood CSF barrier, and displays a connected monolayer of epithelial cells that selects the contents from the blood that reach the brain playing a key role in brain homeostasis. In order to have a deeper understanding about the role of the CP in brain development, it is necessary to investigate the CP cell type composition and cellular states throughout several developmental timepoints, which can be performed by transcriptomic analysis. Single-cell RNA-sequencing (scRNA-seq) is a revolutionary technology for transcriptome analysis as it allows a high throughput single-cell gene expression profiling from a tissue. This technique also provides data to infer cellular differentiation and future transcriptomic states. In this work, the CP transcriptome was analysed in three different timepoints (two postnatal stages and one adult) by two techniques bulk RNA-seq and scRNA-seq. While scRNA-seq analysis in the CP allowed the identification of all cell types that compose the CP as well as some differences in the expression profile between the different CP stages, bulk RNA-seq data allowed an overall analysis of the tissue transcriptomics exhibiting a more pronounced differential gene expression analysis between CP stages. Bulk RNA-seq data analysis demonstrated that CP cells at earlier stages are enriched in genes associated with cell division (Tuba1a, Cul) and cell adhesion (Tubb, Actb, Col4a1) while in adulthood CP was enriched in genes associated to lipid and mitochondrial pathways, such as Ascl3 and Cox8b, respectively. Importantly, scRNA-seq data analysis not only confirmed part of the bulk RNA-seq data but also lead to the identification of a subgroup in epithelial cells that expressed ciliogenesis genes in the early stages of development. Furthermore, the differentially expressed genes uncovered by bulk RNA-seq were assigned to cell types in scRNA-seq. This study unravels several pathways enriched in developmental stages that will be investigated in the future for their role in brain development modulation.
Autores principais:Pacheco, Miguel Monteiro
Assunto:Bulk RNA-seq Choroid Plexus Mus musculus Rattus norvegicus Single-cell RNA-seq Plexo Coróide
Ano:2022
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:The choroid Plexus (CP) is a brain tissue responsible for the production and secretion of the cerebrospinal fluid (CSF). It lays at the interface of the peripheral blood and the brain, forming the blood CSF barrier, and displays a connected monolayer of epithelial cells that selects the contents from the blood that reach the brain playing a key role in brain homeostasis. In order to have a deeper understanding about the role of the CP in brain development, it is necessary to investigate the CP cell type composition and cellular states throughout several developmental timepoints, which can be performed by transcriptomic analysis. Single-cell RNA-sequencing (scRNA-seq) is a revolutionary technology for transcriptome analysis as it allows a high throughput single-cell gene expression profiling from a tissue. This technique also provides data to infer cellular differentiation and future transcriptomic states. In this work, the CP transcriptome was analysed in three different timepoints (two postnatal stages and one adult) by two techniques bulk RNA-seq and scRNA-seq. While scRNA-seq analysis in the CP allowed the identification of all cell types that compose the CP as well as some differences in the expression profile between the different CP stages, bulk RNA-seq data allowed an overall analysis of the tissue transcriptomics exhibiting a more pronounced differential gene expression analysis between CP stages. Bulk RNA-seq data analysis demonstrated that CP cells at earlier stages are enriched in genes associated with cell division (Tuba1a, Cul) and cell adhesion (Tubb, Actb, Col4a1) while in adulthood CP was enriched in genes associated to lipid and mitochondrial pathways, such as Ascl3 and Cox8b, respectively. Importantly, scRNA-seq data analysis not only confirmed part of the bulk RNA-seq data but also lead to the identification of a subgroup in epithelial cells that expressed ciliogenesis genes in the early stages of development. Furthermore, the differentially expressed genes uncovered by bulk RNA-seq were assigned to cell types in scRNA-seq. This study unravels several pathways enriched in developmental stages that will be investigated in the future for their role in brain development modulation.