The human tissue specific proteomeAll, approximately 20000, human genes are classified according to their expression across a large number of tissues representing all major organs and tissue types in the human body. The genes with an elevated expression in a particular tissue are interesting as a starting point to understand the biology and function of this part of the human body, although only a few of these genes show a strict expression in a single tissue or organ.
Specificity illustrates the number of genes with elevated or non-elevated expression. Elevated expression includes three subcategory types:
Distribution, on the other hand, visualizes how many genes that have, or do not have, detectable levels (NX≥1) of transcribed mRNA molecules. As evident in Table 1, all elevated genes are categorized as:
A. Specificity B. Distribution Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in all 37 analyzed tissues. (B) The distribution of all genes across the six categories based on transcript detection (NX≥1) in all 37 analyzed tissues.
The amount of tissue elevated genes is highly variable between the analyzed tissue types (see Table 2 below). Testis shows the largest number of tissue enriched genes (n=950), followed by brain (n=488) and liver (n=242). The large number of enriched genes in testis is considered to be due to the highly specialized processes occurring during spermatogenesis. Also, it is likely that many of these genes have a shared expression with oocytes in the female ovaries. However, oocytes are difficult to analyze because of the complex kinetics of female germ cell development, including first rounds of meiosis, which in females occur at the embryonic stage. Some tissues have similar functions and tissue morphology and as expected, tissue elevated genes in these tissues are predominantly group enriched genes exemplified by lymphoid tissues and the gastrointestinal tract. In addition to previously known proteins, the analysis also identified a large number of genes with tissue elevated expression patterns that were previously poorly characterized and with no or only scarce evidence of existence at protein level. The combined RNA and antibody-based profiling can thus be used to confirm physiological functions of such protein coding genes lacking previous annotation. These proteins are interesting starting points for further in-depth studies to gain a better understanding of the molecular mechanisms of the various cellular phenotypes that define the function of each respective tissue and organ.
Tissue enriched genesThe comprehensive analysis presented here has identified approximately 2845 human genes that display a tissue enriched expression pattern across the human body. A functional analysis revealed that the overall function of a tissue was highly associated with the function of the proteins encoded by the genes enriched in that tissue. The antibody-based protein profiling using immunohistochemistry allows for localization of the proteins corresponding to the different tissue enriched genes, and provides a precise map of protein expression in the various compartments and cell types that constitute different tissues and organs. Examples of tissue type specific proteins with a direct link to tissue function are presented below.
Brain
Retina
Pituitary gland
Kidney
Liver
Pancreas
Male tissues
Female tissues
Skin
Group enriched proteinsThe 1637 genes identified with a group enriched expression pattern reflect genes with shared expression in a limited number of tissues. The function of the corresponding proteins may be involved in various traits that can be shared between cell types located in different tissues and organs, such as proteins expressed in immune cells (various lymphoid tissues), proteins involved in squamous differentiation (esophagus and skin), glandular cell function in the gastrointestinal tract (duodenum, small intestine and colon) or cilia movement (testis and fallopian tube). The schematic network plot below shows the distribution between group enriched genes in different tissues. Figure 3. An interactive network plot of the tissue enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of tissue 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.
Squamous epithelium is found in many parts of the body as dry skin or wet mucosa, acting as a robust barrier against various chemical and mechanical stresses. Desmocollin 3, DSC3, coding for a protein important in cell-cell junctions and cellular adhesion, is group enriched in epithelium tissues, such as esophagus and skin exemplified below. Mucus has several functions in the body related to transportation and barrier functions. The function of the mucus in the salivary gland is related to food and pathogens, while the mucus in the cervix is involved in for example transportation and blockage of sperm during sexual reproduction. MUC16 is a mucus component and is group enriched in both the mucus-producing salivary gland and cervix.
The fallopian tube shares many elevated genes with testis. The common denominator is the utilization of cilia, or the structurally similar flagellum, for essential organ functions. DNAI2, a dynein protein, constitute a motor protein component of motile cilia of multiciliated cells as well as the flagellum (tail) of the sperm. By pulling on the microtubule structure of the cilium/flagellum, the motor protein creates motion and in the case of the sperm, sperm motility. In the IHC images below, expression of DNAI2 can be seen in a subset of cilia in the fallopian tube (left and middle image), as well as in the flagellum of spermatids and cytoplasm of differentiating spermatocytes (right image).
Tissue enhanced genesThe category “tissue enhanced genes” is defined as genes that do not fulfill the criteria of tissue enriched but show a 5-fold higher TPM level in a specific tissue type compared to the average TPM value of all 37 analyzed tissue types. Examples of protein expressionBelow are examples of protein expression patterns of mainly known and well characterized elevated genes in the different parts of the body. Brain
Endocrine tissues
LungProximal digestive tract
Gastrointestinal tract
Pancreas
Liver & gallbladder
Kidney & urinary bladder
Male tissues
Female tissues
Muscle tissues
Adipose & soft tissue
SkinBone marrow
Lymphoid tissue
Relevant links and publications Uhlén M et al, 2015. Tissue-based map of the human proteome. Science Microscopical images of normal tissue - Tissue Dictionary (Human Protein Atlas) |
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