The choroid plexus-specific proteome

The choroid plexus transcriptome

Transcriptome analysis of the choroid plexus can be visualized with regard to the specificity and distribution of transcribed mRNA molecules (Figure 1). Specificity illustrates the number of genes with elevated or non-elevated expression in the choroid plexus compared to other tissues. Elevated expression includes three subcategory types of elevated expression:

• Tissue enriched: At least four-fold higher mRNA level in choroid plexus compared to any other tissues.
• Group enriched: At least four-fold higher average mRNA level in a group of 2-5 tissues compared to any other tissue.
• Tissue enhanced: At least four-fold higher mRNA level in choroid plexus compared to the average level in all other tissues.

Distribution, on the other hand, visualizes how many genes have, or do not have, detectable levels (nTPM≥1) of transcribed mRNA molecules in the choroid plexus compared to other tissues. As evident in Table 1, all genes elevated in choroid plexus are categorized as:

• Detected in single: Detected in a single tissue
• Detected in some: Detected in more than one but less than one-third of tissues
• Detected in many: Detected in at least a third but not all tissues
• Detected in all: Detected in all tissues

Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in choroid plexus as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (nTPM≥1) in choroid plexus as well as in all other tissues.

As shown in Figure 1, 464 genes show some level of elevated expression in the choroid plexus compared to other tissues. The three categories of genes with elevated expression in choroid plexus compared to other organs are shown in Table 1. In Table 2, the 12 genes with the highest enrichment in choroid plexus are defined.

Table 1. The number of genes in the subdivided categories of elevated expression in choroid plexus.

Table 2. The 12 genes with the highest level of enriched expression in choroid plexus. "Tissue distribution" describes the transcript detection (nTPM≥1) in choroid plexus as well as in all other tissues. "mRNA (tissue)" shows the transcript level in choroid plexus as nTPM values. "Tissue specificity score (TS)" corresponds to the fold-change between the expression level in choroid plexus and the tissue with the second-highest expression level.

Gene expression shared between choroid plexus and other tissues

There are 187 group enriched genes expressed in choroid plexus. Group enriched genes are defined as genes showing a 4-fold higher average level of mRNA expression in a group of 2-5 tissues, including choroid plexus, compared to all other tissues.

To illustrate the relation of choroid plexus tissue to other tissue types, a network plot was generated, displaying the number of genes with a shared expression between different tissue types.

Figure 2. An interactive network plot of the choroid plexus enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of choroid plexus enriched genes and orange nodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up to 3 tissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.

Choroid plexus shares most group enriched gene expression with other brain regions, but it also shares some group enriched gene expression with testis, fallopian tube and retina.

Although choroid plexus is a highly specialized tissue within the brain ventricular system with significant differences to other types of brain tissue, it still shares elevated expression of many genes with other brain regions. Examples of these genes includes metallothionein 3 (MT3), encoding a metal-binding protein involved in neuronal zinc and copper homeostasis, and FAM107A and ERMN, encoding two actin-binding proteins that plays important roles in the generation of neuronal projections by forming actin bundles and myelin sheaths, respectively.

MT3 - cerebral cortex
FAM107A - cerebellum
ERMN - caudate

A significant portion of choroid plexus tissue is made up by ependymal cells with motile cilia projecting out towards the ventricular space. Motile cilia are also present on the luminal surface of ciliated cells in the fallopian tubes and exists as a similar structure in the tail (flagella) of sperm in testis. This explains the expression of cilium/flagella-associated genes like; Radial spoke head component 4A (RSPH4A), Dynein axonemal heavy chain 12 (DNAH12), and Leucine rich repeat containing 18 (LRRC18). Choroid plexus also shares elevated expression of genes with retina, including Crumbs cell polarity complex component 2 (CRB2), involved in multiple functions related to retinal neuroepithelium function and seen expressed mainly in membranes of cells in retina and the CNS.

RSPH4A - fallopian tube
DNAH12 - fallopian tube

LRRC18 - testis
CRB2 - retina

Choroid plexus anatomy and function

The choroid plexus comprise capillary-dense tissue structures that are found in all of the ventricles of the brain, projecting into the cerebrospinal fluid (CSF) that fills up the ventricular space. The main function of choroid plexus is to produce and maintain the balanced composition of CSF, a liquid that is necessary to maintain nervous system function. Blood components are filtered out of the local capillaries through endothelial cells and into the local tissue where it is processed by ependymal cells and subsequently excreted into the venctricular space as CSF. Leakage of blood components into the CSF is prevented by ependymal cell tight junctions. Since only compounds necessary for CSF-production are allowed into to the CSF, choroid plexus is called the Blood-CSF barrier.

Choroid plexus is made up by capillaries supported in stroma with an outer coat of ciliated ependymal cells facing the ventricular space.

Background

Here, the protein-coding genes expressed in choroid plexus are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in choroid plexus.

Transcript profiling was based on a combination of two transcriptomics datasets (HPA and GTEx), corresponding to a total of 14590 samples from 54 different human normal tissue types. The final consensus normalized expression (nTPM) value for each tissue type was used for the classification of all genes according to the tissue-specific expression into two different categories, based on specificity or distribution.

Relevant links and publications

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Fagerberg L et al., Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. (2014)
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600