Gene Expression and Functional Annotation of the Human and Mouse Choroid Plexus Epithelium

Abstract

BackgroundThe choroid plexus epithelium (CPE) is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF), which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE.MethodsWe performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data.ResultsOverall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural) developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE.ConclusionHuman and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE between mouse and man differ with respect to transport and metabolic functions.

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

“…These animal models have been used to investigate the sites of microbial entry (20,(102)(103)(104)(105)(106) and the roles of virulence determinants in CNS invasion and pathogenesis (107)(108)(109)(110)(111). Despite clear differences in the size and complexity of mouse and human brains, comparative transcriptomic studies between mice and humans have demonstrated that gene expression profiles of the healthy brain and choroid epithelium are highly conserved between the species (112)(113)(114).…”

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

“…In contrast to the BBB, formed by the nonfenestrated endothelial cells that contain TJs, the choroidal endothelium is fenestrated and lacks TJs, allowing free communication of the CP stroma with the peripheral blood [15,20]. Recently, the transcriptomes of healthy human and mouse CPE were analyzed [25]. Despite the few differences with respect to transport and metabolic functions, the transcriptomes of human and mouse CPE are similar and display common functionalities, proving the relevance of mouse models to the study of the CP in human neuroinflammatory diseases [25].…”

Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

“…The study also showed that while the CP has a unique transcriptome signature, it most closely resembles the BBB (Marques et al, 2011). Other transcriptome studies have demonstrated that the human and mouse CP are very similar in gene expression suggesting that they may also function in a similar manner (Janssen et al, 2013). Recent microarray data comparing adult human and mouse CP showed that there are no genes in human that are not expressed mice, although a few genes in mice are not in human (Janssen et al, 2013).…”

“…Other transcriptome studies have demonstrated that the human and mouse CP are very similar in gene expression suggesting that they may also function in a similar manner (Janssen et al, 2013). Recent microarray data comparing adult human and mouse CP showed that there are no genes in human that are not expressed mice, although a few genes in mice are not in human (Janssen et al, 2013). The major difference between species in regard to CP function was that in mice, the CP is also responsible for carbohydrate metabolism and has a more significant role in development of the brain and eye (Janssen et al, 2013).…”

“…Recent microarray data comparing adult human and mouse CP showed that there are no genes in human that are not expressed mice, although a few genes in mice are not in human (Janssen et al, 2013). The major difference between species in regard to CP function was that in mice, the CP is also responsible for carbohydrate metabolism and has a more significant role in development of the brain and eye (Janssen et al, 2013). Also, a transcriptome analysis of the CP in early development compared to adults has shown that the expression in a large number of genes do not vary between ages suggesting that even early on, the CP is a functional organ (Liddelow et al, 2012).…”