The tongue-specific proteome

The tongue transcriptome

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

• Tissue enriched: At least four-fold higher mRNA level in tongue 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 tongue compared to the average level in all other tissues.

Distribution, on the other hand, visualizes how many genes that have, or do not have, detectable levels (NX≥1) of transcribed mRNA molecules in the tongue compared to other tissues. As evident in Table 1, all genes elevated in tongue 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 tongue as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (NX≥1) in tongue as well as in all other tissues.

As shown in Figure 1, 375 genes show some level of elevated expression in the tongue compared to other tissues. The three categories of genes with elevated expression in tongue compared to other organs are shown in Table 1. In Table 2, the 11 enriched genes are defined.

Table 1. Number of genes in the subdivided categories of elevated expression in tongue.

Table 2. The 11 genes with enriched expression in tongue. "Tissue distribution" describes the transcript detection (NX≥1) in tongue as well as in all other tissues. "mRNA (tissue)" shows the transcript level in tongue as NX values. "Tissue specificity score (TS)" corresponds to the fold-change between the expression level in tongue and the tissue with second highest expression level.

Gene expression shared between tongue and other tissues

There are 165 group enriched genes expressed in tongue. 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 tongue, compared to all other tissues.

In order to illustrate the relation of tongue tissue to other tissue types, a network plot was generated, displaying the number of genes with shared expression between different tissue types.

Figure 2. An interactive network plot of the tongue enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of tongue 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 4 tissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.

Tongue shares most group enriched gene expression with skeletal muscle. It also shares group enriched gene expression with the heart, skin, lymphoid tissue and esophagus - all of which represent different structures found in the tongue.

A major part of tongue tissue consists of muscle fibers also present in the heart and skeletal muscle. This explains the expression of genes like; Actin alpha 1 ACTA1, Myomesin 1 MYOM1, and Sarcalumenin SRL. Another organ tongue has group enriched gene expression in common with is skin. This is due to both tissue types expressing several endothelial specific genes, for example; KLK5, Keratin 14 (KRT14) and -75 (KRT75). Other tissues tongue have group enriched gene expression in common with is the esophagus and lymphoid tissue. Some examples of these genes are; Transglutaminase 1 (TGM1), Alcohol dehydrogenase 7 (ADH7) and Keratin 4 (KRT4).

ACTA1 - skeletal muscle
MYOM1 - heart muscle
SRL - skeletal muscle

KLK5 - skin
KRT14 - skin
KRT75 - skin

TGM1 - esophagus
ADH7 - tonsil
KRT4 - esophagus

Tongue anatomy and function

The tongue is a muscular organ mainly composed of skeletal muscle located in the oral cavity responsible for the ability to swallow, taste and speak. It is composed of interlacing skeletal muscle, pockets of adipose and connective tissue (with mucus and serous glands) covered in oral mucosa.

As previously mentioned the human tongue is composed of eight muscles; 4 intrinsic and 4 extrinsic, and attached to the hyoid bone, mandible, styloid process, palate and pharynx. Furthermore, the tongue is often divided into sections. The right and left side of the tongue are separated by a section of fibrous tissue known as the lingual septum. It is further divided into an anterior and posterior part which are structurally and developmentally distinct. The dorsal surface of the anterior part makes up roughly two-thirds of tongue length while the posterior part consists of the remaining one-third. The anterior two-thirds of the tongue consists of a type of oral mucosa called masticatory mucosa which is made up by keratinized stratified squamous epithelium.. Embedded in the masticatory mucosa are numerous lingual papillae containing taste buds and taste receptors. The ventral surface of the anterior tongue consists of smooth stratified squamous non-keratinized epithelium. Located here are the lingual tonsils which are a collection of nodular lymphatic tissue.

The papillae on the anterior tongue come in four types; filiform, fungiform, foliate and circumvallate. The filiform papillae are the most numerous and cover all of the anterior of the tongue’s surface. They are small cone-shaped structures with keratinized epithelial prolongations which give the tongue its typical texture and which contain many nerves. They are the only papillae not containing any taste buds. Fungiform papillae are mushroom-shaped, nonkeratinized projections, situated mainly on the tip of the tongue, with taste buds on the upper surface. Lastly, there are the foliate papillae which are leaf-shaped and reside on the posterior edges of the tongue. Far back on the anterior two-thirds of the tongue, lining the terminal sulcus, are 3-13 circumvallate papillae. These 1-2mm big papillae are shaped like a dome surrounded by a horseshoe-shaped cleft. The cleft is lined with taste buds and in the bottom, the ducts from the von Ebner’s glands empty their contents. Von Ebner’s gland secretion contains lingual lipase which starts the hydrolysis of lipids in the mouth as well as flushes material from the taste buds to enable fast response to changing stimuli.

As mentioned, located on the base of the posterior part of the tongue are the lingual tonsils. These tonsils are two small aggregations of lymphatic tissue that assist the immune system in the production of antibodies in response to invading pathogens. A thin capsule of connective tissue separates them from adjacent structures.The surface of the tonsils is covered by stratified squamous non-keratinized epithelium and has pits that lead to the lower lymphatic tissue. Contrary to the palatine- and pharyngeal tonsils, the lingual tonsils do not often get inflamed. This is due to mucus glands located at the root of the tongue which drains into their crypt. These secretions from the mucous glands help keep the crypt clean and make them less prone to infection.

Background

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

Transcript profiling was based on the FANTOM5 transcriptomics dataset, corresponding to a total of 77 mixed patient samples from 60 different human normal tissue types. The final consensus normalized expression (NX) value for each tissue type was used for 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

Yu NY et al., Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res. (2015)
PubMed: 26117540 DOI: 10.1093/nar/gkv608

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