The squamous epithelial cell-specific proteomeThe squamous epithelial cell transcriptomeApical squamous epithelial cellsSuprabasal cellsSquamous epithelial cell functionBackgroundRelevant links and publications

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Single cell type methods

The squamous epithelial cell-specific proteome

Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in squamous epithelial cells and 1287 of these genes show an elevated expression in any squamous epithelial cells compared to other cell type groups. In-depth analysis of the elevated genes in squamous epithelial cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in the following types of squamous epithelial cells: Esophageal apical cells, Esophageal suprabasal cells and Subrabasal keratinocytes. Basal cells are separated from other parts of the squamous epithelia and grouped with other basal cells for the general categorization.

The squamous epithelial cell transcriptome

The scRNA-seq-based squamous epithelial cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific squamous epithelial 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 squamous epithelial cell types compared to other grouped cell types.

Apical squamous epithelial cells

Apical squamous epithelial cells are superficial cells at the luminal surface of the esophagus. They provide a protective barrier against mechanical stress and abrasion.

As shown in the table, 1848 genes show elevated expression level in esophageal apical cells compared to other cell types. Serine peptidase inhibitor Kazal type 7 (SPINK7) is an example of a protein with elevated expression in the apical squamous epithelial cells.

SPINK7 - esophagus
SPINK7 - esophagus
SPINK7

Suprabasal cells

Suprabasal keratinocytes are post-mitotic cells that reside in the stratum spinosum-layer of the squamous epithelial cell layer, where they keep differentiating, developing a larger cytoplasm and well-formed bundles of keratin intermediate filaments as they are pushed towards the stratum corneum.

Esophageal suprabasal cells

Esophageal suprabasal cells are differentiated squamous cells located above the basal layer of the esophagus. They contribute to barrier function and resist food‑related friction. As shown in the table, 813 genes show elevated expression level in esophageal suprabasal cells compared to other cell types

CRABP2 - esophagus
CRABP2 - esophagus
CRABP2 - esophagus

Suprabasal keratinocytes

Suprabasal keratinocytes are differentiated epidermal keratinocytes located above the basal layer. They form the stratified barrier and produce structural proteins for skin protection. As shown in the table, 409 genes show elevated expression level in suprabasal keratinocytes compared to other cell types. Examples of proteins expressed in the stratum spinosum include keratin 10 (KRT10), which plays a role in the establishment of the epidermal barrier on plantar skin.

KRT10 - skin
KRT10 - skin
KRT10 - skin

Squamous epithelial cell function

Epithelial cells form sheets of cells, epithelia, that line the outer and inner surfaces of the body and constitute the building blocks for glandular tissues. Hence, epithelial cells are found in many parts of the body, including skin, airways, the digestive tract, glandular tissues and organs, as well as the urinary and reproductive systems. The wide range of functions of epithelial cells can be broadly divided into two main categories, being in charge of the transfer of compounds in or out of the body, as well as being a protective barrier against invading pathogens and physical, chemical or biological abrasion.

To withstand the wear and tear from the environment, the epithelial cells form multilayered (stratified) squamous epithelia that are able to handle consistent abrasion. There are two types of stratified squamous epithelia: the dry keratinized type found in the top layer (epidermis) of skin and the moist non-keratinized type found lining the surface of inner cavities such as the mouth, esophagus and vagina. Squamous epithelia consist of multiple layers of cells, with superficial layers of squamous (flat) cells and underlying replenishing cells. The innermost layer of epithelial cells, in contact with the underlying basal membrane, consists of cuboidal multipotent stem cells, called basal cells. Basal cells divide to renew the entire epithelial lining which is under repeated stress and abrasion from the environment causing the superficial layers to slough off. The daughter cells of basal cells slowly transition into squamous cornified (rigid) dead cells with a high content of keratin filaments as they become increasingly superficially located.

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

Background

Here, the protein-coding genes expressed in squamous epithelial 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 squamous epithelial 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

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

He S et al., Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs. Genome Biol. (2020)
PubMed: 33287869 DOI: 10.1186/s13059-020-02210-0

Solé-Boldo L et al., Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming. Commun Biol. (2020)
PubMed: 32327715 DOI: 10.1038/s42003-020-0922-4