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The skin cell type enriched transcriptomeThe main function of the skin is to protect the body from environmental challenges, such as UV radiation and infectious agents. The skin also regulates body temperature and can detect different sensations like heat, cold, pressure, contact and pain. The skin is divided into two sections, the dermis and the epidermis. The epidermis is the outermost layer of the skin, and is a stratified squamous epithelium primarily composed of keratinocytes, that forms a thick, protective, waterproof layer, both preventing water loss from the body and protecting the underlying dermis from external physical, chemical, and biological insults. The dermis lies below the epidermis, and contains connective tissue and stromal cells, as well as mechanoreceptors, hair follicles, and glands, that provide the ability to sense touch and heat, and to secrete substances to the skin surface. 2519 genes were predicted to have cell type specificity in the skin. Skin cell type enriched transcriptome: SummaryGenes with predicted cell type specificity within skin are detailed in Table 1. Identified genes are subdivided into 3 specificity categories, based on the difference between the enrichment score in the corresponding cell type, compared to the other cell types profiled in the tissue (see Methods Summary page for details):
Skin cell type enriched transcriptome: Illustrative examplesMitotic cellsMitotic cells are highly proliferative stem cells at the base of the epidermal layer that are constantly proliferating in order to renew the upper layers of the skin epidermis. Nucleolar And Spindle Associated Protein 1 (NUSAP1) is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization. Marker Of Proliferation Ki-67 (MKI67) is a nuclear protein that is associated with, and may be necessary for, cellular proliferation. Cyclin B1 (CCNB1) is a regulatory protein involved in mitosis.
Keratinocytes (other)Keratinocytes undergo several stages of development as they differentiate. Basal keratinocytes are the youngest keratinocytes, located at the base of the epidermis, from where they differentiate into mature keratinocytes as they are pushed closer to the surface of the skin by the proliferating cells beneath them. As they differentiate, the cells undergo keratinization, where they expand and produce large amounts of organized keratin filaments as they are pushed closer to the surface of the skin. Desmoglein 1 (DSG1) is a cadherin-like transmembrane glycoprotein, which is a major component of the desmosome. Desmosomes are cell-cell junctions that help withstand shearing forces and tend to be found in high levels in cells that are subject to mechanical stress. Tumor Protein P63 (TP63) is a member of the p53 family of transcription factors, which has an implicated role in skin development and maintenance. Transcription Factor AP-2 Alpha (TFAP2A) is a transcriptional regulator.
Keratinocytes (granular)Granular keratinocytes are terminally differentiated keratinocytes near the top of the epidermis, the keratin matrix and connections with adjacent cells become tighter, and they secrete lipids and proteins to form a hydrophobic, waterproof barrier. They also begin the process of organized cell death as they shed their nuclei and other organelles, migrating into the upper, cornified layer of dead, non-transcriptional, cells that are the outermost barrier against the outside environment. Aspartic Peptidase Retroviral Like 1 (ASPRV1) is a structural protein that is crucial for in the development and maintenance of the skin barrier. Keratinocyte Proline Rich Protein (KPRP) is proline-rich skin protein implicated in keratinocyte differentiation. Ribonuclease A Family Member 7 (RNASE7) belongs to the pancreatic ribonuclease family and has broad-spectrum antimicrobial activity against bacteria and fungi.
MelanocytesMelanocytes are located in the basal layer of the epidermis, and their main function is to produce melanin, a dark pigment that absorbs UV radiation and protects other cells from its mutagenic properties. Melanocytes can also produce and secrete other signal molecules, and may have some functions in immune system management. G Protein-Coupled Receptor 143 (GPR143) binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. Premelanosome Protein (PMEL) is a melanocyte-specific type I transmembrane glycoprotein which is enriched in melanosomes, which are the melanin-producing organelles in melanocytes. Dopachrome Tautomerase (DCT) is an enzyme involved in melanin biosynthesis.
Hair cortex cellsThe hair consists of three layers, the medulla, cortex, and cuticle. The medulla forms a central core, and is surrounded by the cortex, the thickest layer, which consists of many compressed, keratinized cells, followed by the outermost layer; the cuticle, a very hard, thin, layer of keratinized cells that protects the lower layers. The cortex layer makes up the majority of the hair diameter, and contributes most of the color, structure and strength of the hair itself. Keratin Associated Protein 3-3 (KRTAP3-3) is a member of the keratin-associated protein family; these proteins form a matrix of keratin intermediate filaments that contribute to the structure of hair fibers. Keratin 34 (KRT34) is a type I (acidic) hair keratin, which heterodimerizes with type II keratins to form hair and nails. Keratin 86 (KRT86) is a type II keratin protein, which heterodimerizes with type I keratins to form hair and nails.
Inner root sheath cellsThe inner root sheath of the hair follicle forms a rigid, protective covering around the lower portion of the hair follicle shaft. It is essential for the keratinization and shaping of the growing hair, as well as assisting in the adherence of the hair to the base of the shaft, preventing it from loosening or deforming. Keratin 27 (KRT27), a member of the type I (acidic) keratin family, is essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath. Keratin 26 (KRT26) is also a type I keratin, which is specific for the inner root sheath of the hair follicle. Fatty Acid Binding Protein 9 (FABP9) is possibly linked to transporter activity and lipid binding, but its function is not well characterized.
Outer root sheath cellsThe outer root sheath of the hair follicle surrounds the entire hair follicle shaft, and is continuous with the basal layer of the epidermis. It also contains a small stem cell progenitor niche, and is the site of attachment for erector hair smooth muscle cells. Transcriptional Repressor GATA Binding 1 (TRPS1) is a transcription factor most well studied in the context of its role in the regulation of genes that control the growth of bone and cartilage, but it has been also been identified as a regulator of epithelial proliferation in the developing hair follicle.
Sebaceous gland cellsSebaceous glands are exocrine glands located in hair follicles, that secrete an oily or waxy substance called sebum. Sebum lubricates and protects the surface of the hairs and skin, and contributes to the skin’s waterproof properties, both reducing water loss from within the body, and repelling external water. Glycine Decarboxylase (GLDC) is an enzyme active in part of the glycine cleavage system and Sterol O-Acyltransferase 1 (SOAT1) catalyzes the formation of fatty acid-cholesterol esters.
Eccrine sweat gland cellsEccrine sweat gland cells, are present in the dermis of the skin all over the body, and are responsible for secretion of sweat, which coats the surface of the skin and cools the body, regulating body temperature. The secreted sweat is mostly comprised of water and electrolytes, but also contains antimicrobial peptides, such as dermcidin (DCD) that can help protect the skin from infection. Engrailed Homeobox 1 (EN1) has mainly been studied in the context of pattern formation during development of the central nervous system, but its expression has been associated onset of eccrine gland formation. Keratin 19 (KRT19) is a type I keratin.
Langerhans cellsLangerhans cells are a specialized macrophage population resident in the epidermis layer of the skin. They have similarities with both dendritic cells and macrophages, producing proteins typical of both cell types, and presenting antigens to T-cells and migrating to the lymph system in a similar way as dendritic cells. Sialophorin (SPN) is a cell surface sialoprotein, which regulates numerous immune cell functions, most well studied in T-cells. Spi-1 Proto-Oncogene (SPI1) is a transcription factor that activates gene expression during immune cell differentiation or activation. Fc Fragment Of IgG Binding Protein (FCGBP) is a transcriptional activator expressed in intestinal goblet cells and secreted into mucus, its function and role in skin Langerhans cells is unknown.
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