Extended skin tissue samples

The Tissue atlas is based on immunohistochemical staining of tissue microarrays from 44 different normal tissue types. In addition to the standard setup, extended tissue profiling is performed for selected proteins, to give a more complete overview on where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye, thymus and additional samples of adrenal gland, skin and brain. For extended skin samples, both tissue sections and tissue microarrays with 2 mm diameter samples are used for further exploration of proteins expressed in skin, hair, hair follicles, skin, sweat glands and sebaceous glands.

Hair and hair follicles

Hair is found almost everywhere on the body and arises from hair follicles, which are epidermal derivatives present in the connective tissue layer of skin, called dermis. The duration of hair growth (anagen), growth arrest (catagen) and resting periods (telogen) is different throughout the body. Specifically, the growth of hair on the scalp and face is highly influenced by sex hormones, mainly androgens.

The hair can be divided into three layers, namely the medulla, cortex and cuticle layer, all originating from cells at the base of the hair bulb, the dermal papilla. The medulla consists of moderately keratinized cells, while the cortex is formed by compact, heavily keratinized cells, and the surrounding cuticle layer forms a protective layer for the hair shaft. Melanocytes, which are responsible for hair pigmentation, are present in the dermal papilla.

The hair follicle is an epidermal invagination that encloses the initial part of the hair shaft. The hair follicle is composed of two distinct layers: the internal and external root sheath. One example of a protein expressed in the hair follicle is the type II cytoskeletal keratin 71 (KRT71). KRT71 is specifically expressed in the internal root sheath, where it plays a significant role in the formation of hair (Figure 1).

The full list of proteins analyzed in hair and hair follicle samples is found in Table 1.

Figure 1. Immunohistochemical staining of human hair follicles using an antibody toward KRT71 shows strong cytoplasmic staining in the internal root sheath.

Skin glands

As the hair follicles, skin glands also arise from down-growths of epidermal epithelium. The glands are present in the dermis layer of skin and functions in body temperature regulation (eccrine sweat glands) and production of sebum, an oily substance with presumed protective function (sebaceous glands).

The full list of proteins analyzed in sebaceous and sweat gland samples is found in Table 1.

Eccrine sweat glands

Sweat glands are tubular structures in the skin and can be separated into two main types: eccrine sweat glands and apocrine sweat glands. These are different in structure, function, secretory product, mechanism of excretion and distribution in the skin. The eccrine glands can be found throughout the body in varying densities, especially in thick skin, and are primarily involved in the cooling of the human body. The secretory unit is located in the dermis layer and consists of a coiled base that discharges a water-based secretion through a duct, which empties on the surface of the skin. An example of a protein expressed in eccrine sweat glands is dermcidin (DCD), previously known as an antimicrobial peptide important for the innate immune system (Figure 2). The apocrine sweat glands (not included in the analysis) are located at certain parts of the body e.g. armpits, ear canals and eyelids. These glands have also a coiled tubular structure, but empty an oily secretion into hair follicles.

Extended tissue profiling is only assessed in eccrine sweat glands.

Figure 2. Immunohistochemical staining of human skin using an antibody toward DCD shows strong membranous and cytoplasmic positivity in sweat duct cells and secretory cells.

Sebaceous glands

The sebaceous glands are located in the upper part of dermis. Similarly to apocrine sweat glands, they produce an oily or waxy secretion called sebum. One function is to lubricate and protect the hair and skin from water and thus acts as a protective barrier. This barrier function also results in reduction of water loss from skin surface. An example of a protein expressed in sebaceous glands is the elongation of very long chain fatty acids protein 3 (ELOVL3), which plays a role in elongation of long chain fatty acids (Figure 3).

Figure 3. Immunohistochemical staining of human skin using an antibody toward ELOVL3 shows strong cytoplasmic positivity in cells in sebaceous gland.

Table 1. The following 50 genes have been analyzed for expression in hair and hair follicles, skin, sebaceous and sweat glands using extended skin tissue samples.

Gene Gene description Tissue Staining pattern
AWAT1 Acyl-CoA wax alcohol acyltransferase 1 Skin Moderate cytoplasmic staining in a subset of sebaceous cells.
AWAT2 Acyl-CoA wax alcohol acyltransferase 2 Skin Moderate cytoplasmic staining in sebaceous glandular cells.
CD109 CD109 molecule Hair Membrane staining in external root sheath of hair follicle.
DAPL1 Death associated protein like 1 Hair Strong staining in cortex layer.
DCD Dermcidin Skin Strong cytoplasmic and membranous staining in secretory sweat gland cells.
DSC1 Desmocollin 1 Hair Strong in inner root sheath.
DSG4 Desmoglein 4 Hair Strong membranous staining in hair cortex and cuticle.
ELOVL3 ELOVL fatty acid elongase 3 Skin Strong cytoplasmic staining in sebaceous glands.
ELOVL5 ELOVL fatty acid elongase 5 Skin Strong cytoplasmic staining in sebaceous glands.
EN1 Engrailed homeobox 1 Skin Strong nuclear staining in sweat gland secretory cells and ducts.
ERV3-1 Endogenous retrovirus group 3 member 1 Skin Strong staining in sebaceous glands.
FABP9 Fatty acid binding protein 9 Hair Strong cytoplasmic and nuclear staining in the internal root sheath of hair.
GSDMA Gasdermin A Skin Strong cytoplasmic and nuclear staining in sebaceous glands.
GSDMA Gasdermin A Hair Strong staining in hair cortex, cuticle, inner root sheath and inner most layer of external root sheath.
HOXC13 Homeobox C13 Hair Strong nuclear expression in cells in hair cortex, medulla, and in hair follicle external root sheath.
KRT25 Keratin 25 Hair Strong cytoplasmic positivity was observed in internal root sheath of hair follicles.
KRT26 Keratin 26 Hair Strong cytoplasmic staining in inner root sheath of hair.
KRT27 Keratin 27 Hair Distinct staining in internal root sheath.
KRT28 Keratin 28 Hair Strongly stained in internal root sheath of hair follicles.
KRT31 Keratin 31 Hair Strong cytoplasmic staining in hair follicle cortex.
KRT33A Keratin 33A Hair Strong cytoplasmic staining in hair follicle cortex.
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Relevant links and publications

UhlĂ©n M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419

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

Fagerberg L et al, 2014. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics.
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600