The ciliated cell-specific proteomeThe brain and central nervous system coordinate perception, motion, and cognition essential to human life. Their cellular network consists of neurons and supportive glial cells. Glial cells comprise several specialized types with distinct morphology and functions. Among the glial population, there are also specialized ciliated glial cells located along the ventricular walls and within the choroid plexus. These cells contribute to the production, circulation, and regulation of cerebrospinal fluid (CSF), which is essential for maintaining the brain’s chemical environment and protecting neural tissue. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in ciliated cells and 1565 of these genes show an elevated expression in any ciliated cells compared to other brain cell types. Ependymal cells are ciliated cells lining the ventricular system of the brain and central canal of the spinal cord, and choroid plexus epithelial cells are a specialized type of ependymal cells surrounding the network of capillaries that is the choroid plexus, responsible for generating cerebral spinal fluid (CSF). The ciliated cell transcriptomeThe snRNA-seq-based ciliated cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in ciliated cell type compared to other brain cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
Ependymal cellEpendymal cells create a thin, ciliated layer of neuroepithelial tissue that lines the ventricles of the brain and the central canal of the spinal cord. As shown in Table 1, 1029 genes are elevated in ependymal cells compared to other brain cell types. Out of those, 0 genes are also classified as cell type elevated in ciliated cells of other tissue types throughout the body. Since ependymal cells are highly different from other glial cells in the brain, there are high numbers of genes with elevated expression when comparing cells within the brain. And as mentioned, there is a high overlap with markers for ciliated cells, such as STOML3, ANKRD66 and CDHR4 all ciliated enriched and also enriched in ependymal cells in the brain. Additionally, ODAD1 is ciliated enriched in peripheral tissues and classified as group enriched in ependymal cells and choroid plexus epithelial cells of the brain. Thanks to immunohistochemistry we can confirm the location of ciliated proteins in the ependymal cells. CFAP53 and SPAG6 are both classified as group enriched in ependymal cells and choroid plexus epithelial cells, detected at protein level in the ependymal cells present in the caudate nucleus sample, representing basal ganglia of the brain.
Choroid plexus epithelial cellChoroid plexus epithelial cells are a specialized type of ependymal cell, but they exhibit unique characteristics. Choroid plexus cells and ependymal cells form adjacent single-cell layers that meet at a transitional zone. Unlike ependymal cells, the choroid plexus is supported by a basal lamina and possesses barrier properties. Ependymal cells play a vital role in producing and circulating cerebrospinal fluid (CSF), which supports the central nervous system. As shown in Table 1, 784 genes are elevated in Choroid plexus epithelial cells compared to other brain cell types. A serotonin receptor, 5-hydroxytryptamine receptor 2C (HTR2C) is expressed in several clusters of the brain cells, however, shows highest expression level in choroid plexus epithelial cells. Other examples of highly enriched genes are TTR, SLC13A4, KCNJ13 and SLC39A12. The sodium/iodide cotransporter SLC5A5 is highly expressed in choroid plexus epithelial cells, and detected on protein level by immunohistochemistry.
Ciliated cell functionThe histology of organs that contain ciliated cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundSingle nuclei RNAseq dataSiletti K et al. (2023) published single nuclei RNA sequencing result, based on over 3 million cells from multiple brain regions, in Science magazine and created an interactive portal (The Human Brain Cell Atlas v1.0 ) available for single cell exploration across human gene expression in healthy brain cells. The Human Protein Atlas aims to generate a comprehensive resource representing the human body and its complexity, and with a need for better representation of the different cell types of the human brain, we imported the expression profiles and grouped them based on our cell type- strategy (providing bar charts of pooled data for each cell type cluster and calculating the average normalized protein-coding transcripts per million). We based the cell type clusters on the 31 superclusters, as well as the provided assigned cell types, and the data is shown as 34 different "supercluster cell types". The expression profile of the different clusters are shown for each of the 11 different brain regions. More details, related to number of M reads and number of cells per brain region/UMAP can be found here. The published cerebral cortex data is represented by a larger number of cells and we only included a random selection of 500 thousand cells. In total, expression data for 2526725 brain cells is displayed in the Brain single nuclei resource, for browsing the gene expression and provide easy comparison to cell type expression in peripheral tissues.
Relevant publications Uhlén M et al., Tissue-based map of the human proteome. Science (2015) |