The gallbladder-specific proteome
The gallbladder is an organ just under the liver connected to the duodenum, and the purpose of the gallbladder is to store bile, a yellow-brown liquid produced by the hepatocytes in the liver, which enables the digestion of fats. During the storage, water and electrolytes are removed from the bile through an active sodium ion transport across the simple columnar epithelium of the gallbladder, which produces concentrated bile. Transcriptome analysis shows that 75% (n=14840) of all human proteins (n=19670) are expressed in the gallbladder and 161 of these genes show an elevated expression in the gallbladder compared to other tissue types.
The gallbladder transcriptome
Transcriptome analysis of the gallbladder 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 gallbladder compared to other tissues. Elevated expression includes three subcategory types of elevated expression:
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 gallbladder compared to other tissues. As evident in Table 1, all genes elevated in gallbladder are categorized as:
Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in gallbladder as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (NX?1) in gallbladder as well as in all other tissues.
Table 1. Number of genes in the subdivided categories of elevated expression in gallbladder.
Table 2. The 3 genes with enriched expression in gallbladder. "Tissue distribution" describes the transcript detection (NX≥1) in gallbladder as well as in all other tissues. "mRNA (tissue)" shows the transcript level in gallbladder as NX values. "Tissue specificity score (TS)" corresponds to the fold-change between the expression level in gallbladder and the tissue with second highest expression level.
Protein expression of genes elevated in gallbladder
In-depth analysis of the elevated genes in the gallbladder using antibody-based protein profiling allowed us to visualize the expression patterns of these proteins within the gallbladder. The gallbladder is part of the biliary system which refers to the liver, gallbladder and bile ducts. Examples of proteins with elevated expression in the gallbladder include CHST4, MUC5B and TFF1.
Gene expression shared between gallbladder and other tissues
There are 41 group enriched genes expressed in gallbladder. 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 gallbladder, compared to all other tissues.
In order to illustrate the relation of gallbladder 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 gallbladder enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of gallbladder 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.
The main function of the gallbladder is to concentrate, store and release bile into the small intestine. Bile is a yellow-brown liquid produced by the hepatocytes in the liver. The release of bile is stimulated by the presence of dietary fats in the small intestine where it acts as a surfactant to emulsify and digest lipids from the food.
The gallbladder sac is attached to the posterior surface of the right lobe of the liver. It is divided into the fundus, body and neck.
The wall of the gallbladder is composed of three layers: mucosa, muscularis, and serosa. There are no muscularis mucosae or submucosa. The mucosa is made up of branching folds lined by a single layer of columnar cells having a pale cytoplasm. The lamina propria encompasses loose connective tissue, blood vessels, nerves, and sparse plasma cells. The muscularis is made up of randomly distributed smooth muscle fibers.
Here, the protein-coding genes expressed in gallbladder are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in gallbladder.
Relevant links and publications
Uhlén M et al., Tissue-based map of the human proteome. Science (2015)