The ciliated cell-specific proteome

Ciliated cells with motile cilia are found in many parts of the body, including the respiratory epithelium lining the bronchi and bronchioles, and in glandular epithelia of reproductive tissues. Ciliated cells facilitate mucociliary transport of cells and particles needed for the clearance of unwanted particles in the respiratory tract and the transport of gametes and the early embryo during reproduction.

  • 1800 elevated genes
  • 115 enriched genes
  • 478 group enriched genes
  • Main function: Transport substances across epithelial surfaces

Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in ciliated cells and 1800 of these genes show an elevated expression in any ciliated cells compared to other cell type groups. In-depth analysis of the elevated genes in ciliated cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in the following types of ciliated cells: brain, pituitary gland, lung, epididymis, fallopian tube and endometrium.


The ciliated cell transcriptome

The scRNA-seq-based ciliated cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific ciliated cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:

  • Cell type enriched: At least four-fold higher mRNA level in a certain cell type compared to any other cell type.
  • Group enriched: At least four-fold higher average mRNA level in a group of 2-5 cell type groups (out of 53) or 2-15 cell types (out of 154) compared to any other.
  • Cell type enhanced: At least four-fold higher mRNA level in a certain cell type compared to the average level in all other cell types.


Table 1. Number of genes in the subdivided specificity categories of elevated expression in the analyzed ciliated cell types compared to other grouped cell types.

Cell type Tissue origin Cell type enrichedGroup enrichedCell type enhancedTotal elevated
Ciliated cells brain, endometrium, epididymis, fallopian tube, lung 115 478 1207 1800

As shown in Table 1, 1800 genes show elevated expression in ciliated cells, as a group, compared to other grouped cell types. An example of an important protein with elevated expression in ciliated cells is forkhead box J1 (FOXJ1), which is a nuclear transcription factor required for the production of motile cilia. The expression profile of FOXJ1 is observed in ciliated cells across all tissue types included, confirmed at protein level by immunohistochemical stainings.


FOXJ1 - brain non-neurons

FOXJ1 - fallopian tube

FOXJ1 - endometrium

FOXJ1 - lung

FOXJ1 - caudate

FOXJ1 - fallopian tube

FOXJ1 - endometrium

FOXJ1 - bronchus

Expression profiles are compared across the 154 cell types, in addition to the comparison across the 53 grouped cell types. This results in cell specificity categories based on two datasets, one more detailed across all cell types and one more suitable for the general overview based on the grouped cell types with similar expression profile and functions. Cell types are grouped based on function and biology, to facilitate a better overview and to complement the detailed information based on all cell types.

Table 2. Number of genes in the subdivided specificity categories of elevated expression in the different types of ciliated cell types, compared to all other cell types.

Cell type Tissue origin Cell type enrichedGroup enrichedCell type enhancedTotal elevated
Ependymal cells brain 13 124 1251 1388
Choroid plexus epithelial cells brain 15 109 1175 1299
Respiratory ciliated cells lung 2 64 663 729
Respiratory deuterosomal cells lung 4 7 192 203
Epididymal efferent duct ciliated cells epididymis 0 60 456 516
Fallopian tube ciliated cells fallopian tube 0 60 595 655
Endometrial ciliated cells endometrium 0 60 459 519
Any Ciliated cells 34 199 2607 2840


Ependymal cells

The ependymal cells are lining the ventricular system of the brain, it consists of a simple columna ciliated epithelium, with a glial origin of development. Eventhough the ependymal cells are glial cells, their main function involves the apical cilia and ciculation of cerebrospinal fluid (CSF). Ependymal 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 2, 1388 genes show elevated expression in ependymal cells compared to other cell types. An example of a protein with elevated expression in ependymal cells is RSPH4A, also detected in the ependymal cells of caudate using immunohistochemistry.


RSPH4A - brain non-neurons

RSPH4A - brain non-neurons

RSPH4A


Choroid plexus epithelial cells

Choroid 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 2, 1299 genes show elevated expression in choroid plexus epithelial cells compared to other cell types. Examples of genes with enriched expression are SLC13A4, KCNJ13 and SLC39A12. The sodium/iodide cotransporter SLC5A5 is highly expressed in choroid plexus epithelial cells, and detected at protein level by immunohistochemistry.


SLC5A5 - brain non-neurons

SLC5A5 - brain non-neurons

SLC5A5


Respiratory ciliated cells

Respiratory ciliated cells line the airways of the respiratory tract and help clear mucus, dust and pathogenes from the lunchs by moving them towards the throat for expulsion. Their coordinated ciliary movements is essential for keeping the airways clean and protecting agains respiratory infections. As shown in Table 2, 729 genes show elevated expression in respiratory ciliated cells, compared to other cell types. ARMC3 is an example of genes with elevated expression in respiratory ciliated cells.


ARMC3 - lung

ARMC3 - lung

ARMC3 - bronchus


Respiratory deuterosomal cells

Respiratory deuterosomal cells are precursor cells in the respiratory epithelium that generate multiple basal bodies needed for ciliogenesis. They play a key role in the renewal and repair of ciliated cells, especially after airway injury. As shown in Table 2, 203 genes show elevated expression in respiratory deuterosomal cells, compared to other cell types. Cycline O (CCNO) and Cell division cycle 20B (CDC20B) are two examples of genes with enriched expression in deuterosomal cells when comparing to other cell types.


CCNO - lung

CCNO - lung

CDC20B - lung

CDC20B - lung


Epididymal efferent duct ciliated cells

Epididymal efferent duct ciliated cells is located in the male reproductive tract, they help move sperm and fluid through the efferent ducts of the epididymis. Their ciliary motion assists in sperm concentration and transport. As shown in Table 2, 516 genes show elevated expression in epididymal efferent duct ciliated cells, compared to other cell types. An example of a protein elevated in the epididymal efferent duct ciliated cells is cilia- and flagella-associated protein 53 (CFAP53), required for motile cilium formation.


CFAP53 - epididymis

CFAP53 - epididymis

CFAP53 - efferent ducts

Fallopian tube ciliated cells

Fallopian tube ciliated cells are found in the lining of the oviducts, these cells faciliatet the movement of the egg towards the uterus. Their coordinated movment is vital for successful fertilization and early embryo transport. As shown in Table 2, 655 genes show elevated expression in Fallopian tube ciliated cells, compared to other cell types. An example of a protein elevated in the fallopian tube ciliated cells is the cilia apical structure protein, Sentan (SNTN).


SNTN - fallopian tube

SNTN - fallopian tube

SNTN - fallopian tube


Endometrial ciliated cells

Endometrial ciliated cells are present in the uterine lining, these cells help circulate uterine fluid and may assist in creating a favourable environment fr embryo implantation. Their activity fluctuates with the hormonal changes across the menstrual cycle. As shown in Table 2, 519 genes show elevated expression in Endometrial ciliated cells, compared to other cell types. Radial spoke head component 1 (RSPH1) is an example of genes with elevated expression in ciliated cells, including


RSPH1 - endometrium

RSPH1 - endometrium

RSPH1 - endometrium

Ciliated cell function

Ciliated cells are specialized epithelial cells that possess hair-like structures called silia on their surface. These cilia move in coordinated waves to move fluids, particles, or cells along the epithelial surfaces. They play a crucial role in maintaining the cleanliness and function of various organs by faciliatating transport and preventing blockage or infections. Ciliated cells are found throughtoit the body, particularly in the respiratory tract, reproductive system, and central nervous system. A motile cilia is different from primary cilia, involved in sensory and signaling.

The histology of organs that contain ciliated cells, including interactive images, is described in the Protein Atlas Histology Dictionary.


Background

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

The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq and snRNA-seq experiments (36 datasets) covering 34 tissues. All datasets (unfiltered read counts of cells) were clustered independenty using leiden clustering, resulting in a total of 1175 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The RNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding counts per million (nCPM) for all protein-coding genes. A specificity and distribution classification was performed for both single cell types individually, as well as grouped into 53 main cell type groups. The specificity classification determined the number of elevated genes, while the distribution determined whether genes are detected in one, several or all cell types or cell type groups.

It should be noted that since the analysis was limited to datasets representing 34 tissue types, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity.


Relevant links and publications

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Man L et al., Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures. Cell Rep. (2020)
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