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 additional data about where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye, 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 hair, hair follicles, 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.


Table 1. The following 32 genes have been analyzed for expression in hair and hair follicles using extended skin tissue samples.

Gene

Gene description

Staining pattern

DSG4 Desmoglein 4 Strong membranous staining in hair cortex and cuticle.
KRT25 Keratin 25, type I Strong cytoplasmic positivity was observed in internal root sheath of hair follicles.
KRT26 Keratin 26, type I Strong cytoplasmic staining in inner root sheath of hair.
KRT27 Keratin 27, type I Distinct staining in internal root sheath.
KRT28 Keratin 28, type I Strongly stained in internal root sheath of hair follicles.
KRT31 Keratin 31, type I Strong cytoplasmic staining in hair follicle cortex.
KRT33A Keratin 33A, type I Strong cytoplasmic staining in hair follicle cortex.
KRT33B Keratin 33B, type I Strong cytoplasmic staining in hair follicle cortex.
KRT34 Keratin 34, type I Strong cytoplasmic staining in hair follicle cortex.
KRT71 Keratin 71, type II Strong cytoplasmic positivity in inner root sheath.
KRT72 Keratin 72, type II Strong positivity in hair cuticle.
KRT73 Keratin 73, type II Strong cytoplasmic staining in the internal root sheath layer of hair.
KRT75 Keratin 75, type II Moderate cytoplasmic positivity was detected in cells in external root sheath of hair follicles.
KRT79 Keratin 79, type II Strong cytoplasmic staining in external root sheath of hair.
KRT81 Keratin 81, type II Strong cytoplasmic staining in hair cortex/medulla.
KRT82 Keratin 82, type II Strong positivity in hair cuticle.
KRT83 Keratin 83, type II Strong cytoplasmic staining in hair cortex/medulla.
KRT84 Keratin 84, type II Moderate cytoplasmic staining in a subset of cells in external root sheath.
KRT85 Keratin 85, type II Strong cytoplasmic staining in hair cortex/medulla.
KRT86 Keratin 86, type II Strong cytoplasmic staining in hair cortex/medulla.
KRTAP11-1 Keratin associated protein 11-1 Strong positivity in the cortex and medulla of hair follicles.
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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). Apocrine sweat glands are located to 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). The full list of proteins analyzed in sebaceous and sweat gland samples is found in Table 2.

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



Table 2. The following 6 genes have been analyzed for expression in sebaceous and sweat glands using extended skin tissue samples.

Gene

Gene description

Staining pattern

AWAT2 Acyl-CoA wax alcohol acyltransferase 2 Moderate cytoplasmic staining in sebaceous glandular cells.
DCD Dermcidin Strong cytoplasmic and membranous staining in secretory sweat gland cells.
ELOVL3 ELOVL fatty acid elongase 3 Strong cytoplasmic staining in sebaceous glands.
ELOVL5 ELOVL fatty acid elongase 5 Strong cytoplasmic staining in sebaceous glands.
EN1 Engrailed homeobox 1 Strong nuclear staining in sweat gland secretory cells and ducts.
GSDMA Gasdermin A Strong cytoplasmic staining in sebaceous glands.


Relevant links and publications


UhlÚn 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