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The specialized epithelial cell-specific proteomeThe specialized epithelial cell transcriptomeAlveolar cellsBarrier epithelial cellsIonocytesSecretory gland supportDuctal cellsHepatocytesRenal nephron cellsReproductive supporting cellsBasal cellsSpecialized epithelial cell functionBackgroundRelevant links and publications
Single cell type methods
The specialized epithelial cell-specific proteomeEpithelial cells form sheets of cells, epithelia, that line the outer and inner surfaces of the body and constitute the building blocks for glandular tissues. In addition to glandular and squamous epithelial cells, there are several other types of epithelial cells, specialized to the purpose of their environment. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in specialized epithelial cells and 4623 of these genes show an elevated expression in any specialized epithelial cells compared to other cell type groups. In-depth analysis of the elevated genes in specialized epithelial cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in specialized epithelial celltypes. The specialized epithelial cell types includes 38 cell types, grouped into 9 cell type groups, these groups include alveolar cells, barrier epithelial cells, ionocytes, secretory gland support, ductal cells, hepatocytes, renal nephron cells, reproductive supporting cells and basal cells, the number of cell types in respective group varies. The specialized epithelial cell transcriptomeThe scRNA-seq-based specialized epithelial cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific specialized epithelial cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
Expression profiles are compared across the 154 cell types, in addition to the comparison across the 53 grouped cell types. This results in cell specificity categories based on two datasets, one more detailed across all cell types and one more suitable for the general overview based on the grouped cell types with similar expression profile and functions. Cell types are grouped based on function and biology, to facilitate a better overview and to complement the detailed information based on all cell types. Alveolar cellsAlveolar cells type 1, covering 95% of the alveolar wall surfaces and involved in the exchange of carbon dioxide and oxygen between the blood and air in the alveoli. Alveolar cells type 2, located mainly at the junctions between alveolar walls and produce surfactants that are essential for the normal function of alveoli. Table 2. Number of genes in the subdivided specificity categories of elevated expression in alveolar cell types, compared to all other cell types.
Alveolar cells type 1As shown in Table 2, 370 genes show elevated expression in alveolar cells type 1 compared to other cell types. Gas exchange between the air in the lung alveoli and blood takes place via the alveolar cells type 1, which line the alveolar walls. An examples of proteins elevated in alveolar cells type 1 is the advanced glycosylation end-product specific receptor (AGER), a transmembrane receptors with a broad repertoire of ligands associated with inflammation, infection and aging.
Alveolar cells type 2As shown in Table 2, 295 genes show elevated expression in alveolar cell type 2 compared to other cell types. Alveolar cells type 2 are located in lung alveoli and produce surfactants which are crucial for the gaseous exchange between air and blood and for lowering surface tension which prevents alveolar collapse. A gene with enriched expression in alveolar cells type 2 is surfactant protein C (SFTPC), which encodes a surfactant protein. Another example is aspartic peptidase napsin A (NAPSA), a protease that may play a role in the proteolytic processing of surfactant protein B.
Barrier epithelial cellsBarrier epithelial cells form protective layers that separate internal tissues from external or fluid-filled environments, maintaining homeostasis and preventing pathogen invasion. This diverse group, including epicardial, mesothelial, ocular, and urothelial cells, plays essential roles in tissue protection, selective permeability, and organ-specific repair processes. Table 3. Number of genes in the subdivided specificity categories of elevated expression in barrier epithelial cell types, compared to all other cell types.
Ocular epithelial cellsThe ocular epithelial cells protects the eye, maintain a smooth refractive surface, and participate in wound healing. As shown in Table 3, 405 genes show elevated expression in ocular epithelial cells compared to other cell types. Mesothelial cellsMesothelial cells are specialized epithelial cells that form a thin sheet that covers the inner cavities and organs of the body, including the pleural, peritoneal and pericardial cavities. They provide a slippery, protective surface and regulate inflammation and tissue repair. As shown in Table 3, 243 genes show elevated expression in mesothelial cells compared to other cell types. Mesothelial cells in this data set is available from thymus and adipose tissue, where several of the genes with elevated expresson is strongly expressed by mesothelial cells of the thymus, examples are MSLN and ITLN1.
Urothelial cellsUrothelium consists of transitional epithelial cells lining the renal pelvis, ureters, and bladder. They form a stretchable, impermeable barrier that resists urine toxicity. As shown in Table 3, 473 genes show elevated expression in urotheliall cells compared to other cell types. Among the urothelial cell elevated proteins there are several uroplakins, a group of integral membrane proteins that assemble into rigid, crystalline plaques on the apical surface of urothelial cells, often the umbrella cells. Two examples are uroplakin 3A (UPK3A) and uroplakin 2 (UPK2).
Epicardial cellsMesothelial‑derived cells covering the heart that secrete signaling factors during development and repair. They can give rise to fibroblasts and vascular support cells in some contexts. As shown in Table 3, 1010 genes show elevated expression in Epicardial cells compared to other cell types. Prostatic hillock cellsEpithelial cells located near the prostatic urethra (hillocks). Besides protection, they are also thought to act as progenitors and contribute to secretory duct maintenance. As shown in Table 3, 214 genes show elevated expression in prostatic hillock cells compared to other cell types. Prostatic hillock cells exhibit a functional overlap with renal papillary tip epithelial and urothelial cells through shared features such as uroplakin production, epithelial barrier specialization, and resistance to the chemical and mechanical stresses associated with the urinary environment. An example of this is Peptidyl arginine deiminase 3 (PADI3).
IonocytesIonocytes are specialized epithelial cells responsible for regulating ion and fluid balance across epithelial surfaces, maintaining proper electrolyte composition and pH. In both salivary and respiratory tissues, they contribute to secretion and hydration processes essential for mucosal function and overall epithelial health. As shown in Table 1, 130 genes show elevated expression in ionocytes as a group, compared to other grouped cell types. Table 4. Number of genes in the subdivided specificity categories of elevated expression in different ionocytes, compared to all other cell types.
Respiratory ionocytesIonocytes correspond to one percent of all cells in the respiratory epithelium. They maintain an optimal ion concentration in the apical surface fluid essential for cilia motility. As shown in table 4, 163 genes show elevated expression in respiratory ionocytes, compared to other cell types. An example of a protein with elevated expression in ionocytes is Barttin CLCNK type accessory subunit beta (BSND), which is a subunit of CLC chloride channels that transport various ions across the cell membrane.
Salivary ionocytesIon‑transporting epithelial cells in salivary ducts that adjust saliva composition. They fine‑tune electrolyte and fluid balance before secretion into the mouth. As shown in table 4, 156 genes show elevated expression in salivary ionocytes, compared to other cell types. Forkhead box I1 (FOXI1) is a transcription factor with elevated expression in the salivary ionocytes.
Secretory gland supportSecretory gland support cells is amixed group of cells that aid in the production, modulation, and protection of glandular secretions, ensuring efficient function of epithelial tissues. These cells, such as myoepithelial cells, thymic epithelial, Paneth, and tuft cells, contribute to secretion, structural support, immune regulation, and maintenance of the glandular microenvironment. Table 5. Number of genes in the subdivided specificity categories of elevated expression in secretory gland supporting cells, respectively compared to all other cell types.
Salivary myoepithelial cellsContractile cells around acini and ducts that aid saliva expulsion. They also help maintain gland architecture and signaling to acinar cells. 187 genes show elevated expression in salivary myoepithelial cells compared to other cell types. Paneth cellsSpecialized intestinal crypt cells that secrete antimicrobial peptides and support stem cells. They regulate the microbial niche and protect the mucosa. 315 genes show elevated expression in Paneth cells compared to other cell types. An exampled of a protein with elevated expression in paneth cells is DEFA5, an antimicrobial peptide that is part of the innate defence agains pathogens.
Tuft cellsChemosensory epithelial cells with apical microvilli that detect luminal cues. They secrete cytokines and mediators that shape mucosal immunity and type‑2 responses. 439 genes show elevated expression in Tuft cells compared to other cell types. Breast myoepithelial cellsBreast myoepithelial cells are usually found in close proximity to breast glandular cells and are related to smooth muscle cells. The contraction of the myoepithelial cells facilitates the expulsion of the glandular cell secretion. 256 genes show elevated expression in breast myoepithelial cells compared to other cell types. An examples of a protein with elevated expression in breast myoepithelial cells are calponin 1 (CNN1) and myosin light chain kinase (MYLK), both of which are involved in smooth muscle contraction
Medullary thymic epithelial cellsThymic epithelial cells that express tissue‑restricted antigens under AIRE control. They mediate negative selection to establish central tolerance and prevent autoimmunity. 220 genes show elevated expression in Medullary thymic epithelial cells compared to other cell types. Ductal cellsDuct cells are specialized epithelial cells that modify, transport, and regulate the composition of fluids passing through glandular or tubular systems in various organs. Across tissues such as the salivary glands, liver, pancreas, kidney, and epididymis, these cells participate in secretion, absorption, and ion exchange, helping to maintain fluid balance, electrolyte homeostasis, and proper organ function. Despite organ-specific role, like bile modification by cholangiocytes or urine concentration by renal duct cells, they share a common function in fine-tuning and directing the final composition of excreted or secreted fluids. As shown in Table 1, 1051 genes show elevated expression in ductal cells as a group, compared to other grouped cell types. Table 6. Number of genes in the subdivided specificity categories of elevated expression in ductal cells, respectively, compared to all other cell types.
Salivary duct cellsDuctal epithelial cells in the salivary gland can be found throughout the exocrine tissue forming the structure of the gland, guiding the saliva from the acini to the oral cavity. As shown in Table 6,175 genes show elevated expression in salivary duct cells compared to other cell types. An example of a protein found in salivary duct cells with elevated expression compared to other cell types is the nitric oxide generating enzyme nitric oxide synthase 1 (NOS1) which has, among other functions, antimicrobial activity.
CholangiocytesCholangiocytes are the epithelial cells of the bile duct system in the liver that modify and transport bile. They regulate bile volume and composition and participate in liver repair. As shown in Table 6, 204 genes show elevated expression in cholangiocytes compared to other cell types. A gene with enhanced expression in cholangiocytes are for example transcription factor hepatocyte nuclear factor 1-beta (HNF1B)
Pancreatic duct cellsDuctal epithelial cells in the pancreas can be found throughout the exocrine tissue, guiding the secretions from the acini to the duodenum. As shown in Table 3, 202 genes show elevated expression in pancreatic ductal epithelial cells compared to other cell types. Cystic fibrosis transmembrane conductance regulator (CFTR) is an example of a gene with elevated expression in the ductal epithelium of the pancreas. CFTR functions as an ion channel transporting Cl- and HCO3- ions out from the cell in an ATP-dependent manner.
Renal collecting duct intercalated cellsCollecting ducts cells are the main site of salt and water transport, as well as acid-base regulation. They complement principal cells to fine‑tune urine composition. As shown in Table 6, 734 genes show elevated expression in collecting duct intercalated cells compared to other cell types. Renal collecting duct principal cellsTubular cells that reabsorb sodium and water via ENaC and aquaporins under hormonal control. They are key effectors of extracellular fluid volume and potassium balance. As shown in Table 6, 714 genes show elevated expression in collecting duct principal cells compared to other cell types. An example of a protein elevated in collecting ducts principal cells is FXYD domain containing ion transport regulator 4 (FXYD4). It encodes a protein that regulates the transport of ions across the cell membrane.
Renal connecting tubule cellsSegmental tubular cells that continue distal nephron sodium reabsorption and help control calcium and magnesium. They transition toward collecting duct functions. As shown in Table 6, 726 genes show elevated expression in connecting tubule cells compared to other cell types. Epididymal efferent duct absorptive cellsNon‑ciliated epithelial cells that absorb fluid in the efferent ducts. This concentrates sperm and contributes to their maturation environment. As shown in Table 6, 342 genes show elevated expression in epididymal efferent duct absorptive cells compared to other cell types. HepatocytesThe hepatocytes are the main cell type in the liver and responsible for many of the body's metabolic processes as well as the breakdown of toxic substances. As shown in Table 1, 571 genes show elevated expression in hepatocytes compared to other grouped cell types. Although hepatocytes are not grouped for the expression comparison, the category results in a different number due to the comparison to 53 grouped cell types or 154 cell types (table 7). Table 7. Number of genes in the subdivided specificity categories of elevated expression in hepatocytes compared to all other cell types.
905 genes show elevated expression in hepatocytes compared to other cell types. Examples of hepatocyte enhanced genes are retinol dehydrogenase 16 (RDH16) and hydroxyacid oxidase 1 (HAO1) involved in lipid metabolism.
Renal nephron cellsCells of the renal nephron work together to filter blood, reabsorb essential molecules, and concentrate urine to maintain fluid and electrolyte balance. This includes podocytes that form the filtration barrier, proximal and distal tubule cells that handle selective reabsorption and secretion, loop of Henle epithelial cells that regulate water and ion gradients, and papillary tip cells that contribute to final urine concentration. As shown in Table 1, 1298 genes show elevated expression in renal nephron cells as a group, compared to other grouped cell types. Table 8. Number of genes in the subdivided specificity categories of elevated expression in the different cells of the renal nephron, compared to all other cell types.
PodocytesPodocytes are highly specialized glomerular epithelial cells that maintain the filtration barrier and protect against protein loss. As shown in Table 8, 827 genes show elevated expression in podocytes compared to other cell types. An example of a podocyte enriched proteins is podocalyxin (PODXL), a common marker for podocytes and functionally it contributes to the negative charge and structural integrity of the filtration barrier, preventing protein loss into the urine.
Proximal tubule cellsApproximately 60% of the filtered Na+, Cl-, K+, Ca2+, H2O and more than 90% of the filtered HCO3- are absorbed along the proximal tubule. This is also the segment that normally reabsorbs virtually all the filtered glucose and amino acids. An additional function is the secretion of numerous organic anions and cations. As shown in Table 8, 919 genes show elevated expression in proximal tubule cells compared to other cell types. An examples of a protein that show elevated expression in the proximal part of the renal tubules is agmatinase (AGMAT), an enzyme involved in the processing of urea and amino acids.
Loop of henle epithelial cellsThe loop of henle includes nephron segment cells that establish a countercurrent gradient for urine concentration. Thick ascending limb cells reabsorb salts while being impermeable to water. As shown in Table 8, 707 genes show elevated expression in Loop of henle epithelial cells compared to other cell types. An example of a protein with elevated expression in loop of henle epithelial cells is solute carrier family 12 member 1 (SLC12A1), one of several potassium, sodium, and calcium transporters essential for regulating the contents and volume of urine.
Papillary tip epithelial cellsPapillary tip epithelial cells are specialized cells located at the tip of the renal papilla, the region of the kidney where urine drains into the minor calyx. Their main functions include forming a protective barrier against the hyperosmotic and potentially toxic environment of concentrated urine, and regulating water and solute transport at the terminal end of the nephron. As shown in Table 8, 576 genes show elevated expression in Papillary tip epithelial cells compared to other cell types.
Distal convoluted tubule cellsBoth the distal tubule and collecting duct are the sites where critical regulatory hormones such as aldosterone and vasopressin regulate acid and potassium excretion and determine the final urinary concentration of K+, Na+, and Cl-. As shown in Table 8, 768 genes show elevated expression in distal tubular cells compared to other cell types. An example is transmembrane protein 52B (TMEM52B), the function of which is not completely characterized but TMEM52B is highly elevated in distal tubular cells.
Reproductive supporting cellsReproductive supporting cells provide essential structural, metabolic, and regulatory support for gamete development and maturation. In the testis, Sertoli cells nurture developing sperm and form the blood–testis barrier; in the epididymis, principal and clear cells modify the luminal environment to promote sperm maturation and storage; and in the ovary, granulosa cells support oocyte growth, produce sex hormones, and regulate follicle development. Collectively, these cells create and maintain the specialized microenvironments required for successful reproduction. As shown in Table 1, 797 genes show elevated expression in reproductive supporting cells as a group, compared to other grouped cell types. Table 9. Number of genes in the subdivided specificity categories of elevated expression in reproductive supporting cells, respectively, compared to all other cell types.
Sertoli cellsSertoli cells constitute the seminiferous epithelium in testis, interspersed between the germ cells. They play an important role in spermatogenesis, where they are often referred to as nursing cells since their function is to nourish the developing sperm cells. Sertoli cells also play a central role in the control of spermatogenesis by transducing hormonal signals, e.g. activation and stimulation by follicle stimulating hormone (FSH). As shown in Table 9, 599 genes show elevated expression in sertoli cells compared to other cell types. An example of a protein with elevated e epididymal peptidase inhibitor (EPPIN) that has an essential role in male reproduction and fertility by providing antimicrobial protection.
Epididymal clear cellsAcidifying cells rich in V‑ATPase that lower luminal pH in the epididymis. This environment supports sperm storage and maturation. As shown in Table 9, 227 genes show elevated expression in epididymal clear cells compared to other cell types. Epididymal principal cellsThe main epithelial cells of the epididymis that secrete and absorb proteins and ions. They condition sperm membranes and contribute to fertility. As shown in Table 9, 616 genes show elevated expression in epididymal principal cells compared to other cell types. Among the genes with elevated expression in epididymis principal cells are defensins, including DEFB121. Defensins are small antimicrobial peptides that play a crucial role in innate immunity by disrupting microbial membranes and preventing infection. In the epididymis, defensins help protect sperm from pathogens while also contributing to sperm maturation and the maintenance of a balanced luminal environment.
Granulosa cellsGranulosa cells are follicle cells surrounding the oocytes in the ovaries and are believed to originate from ovarian surface epithelium. Their main function is to support the growth and maturation of the oocyte and support eventual pregnancy following ovulation through the production of hormones and growth factors. As shown in Table 9, 218 genes show elevated expression in Granulosa cells compared to other cell types. ELK1 encodes a transcription factor that show enriched mRNA expression in granulosa cells as well as clear nuclear expression in granulosa cells of ovarian follicles.
Basal cellsBasal cells are stem or progenitor-like epithelial cells that reside along the basement membrane of various tissues, providing structural support and serving as a source for cell renewal and regeneration. Found in organs such as the respiratory tract, esophagus, salivary glands, skin, epididymis, and prostate, they play key roles in maintaining epithelial integrity, repairing tissue after injury, and regulating differentiation of specialized luminal cells. In many epithelia, basal cells also contribute to barrier function and cell–cell signaling, helping preserve tissue homeostasis and organization. Table 10. Number of genes in the subdivided specificity categories of elevated expression in basal cells, respectively, compared to all other cell types.
Respiratory basal cellsBasal cells are small stem cells located in the basal part of the respiratory epithelium. They differentiate into the other cell types when the epithelium is injured, thereby restoring the epithelium. As shown in Table 10, 147 genes show elevated expression in basal respiratory cells compared to other cell types. An example of a protein with elevated expression in basal respiratory cells is cadherin 3 (CDH3), which is a member of the cadherin family of proteins involved in calcium-dependent cell adhesion.
Esophageal basal cellsProgenitor cells of the stratified squamous esophageal epithelium. They are highly proliferative and responsible for the renewal of the layers of squamous epithelial cells above. As shown in Table 10, 527 genes show elevated expression in esophageal basal cells compared to other cell types. One protein expressed in the basal layer is Tumor protein p73 (TP73), which is a transcription factor participating in the apototic response to DNA damage. Cadherin 3 (CDH3) is a calcium dependent cell adhesion protein from the cadherin family. CDH3 helps to support epithelial cell layers by interacting in a homophilic manner anchoring the cells together.
Salivary basal cellsBasal epithelial cells that contribute to ductal and acinar turnover. They help maintain glandular structure after injury. As shown in Table 10, 108 genes show elevated expression in Salivary basal cells compared to other cell types. Basal keratinocytesBasal keratinocytes are stem cells found in the basal layer of the epidermis in skin. They are highly proliferative and responsible for the renewal of keratinocytes. As shown in Table 10, 289 genes show elevated expression in basal keratinocytes compared to other cell types.One protein expressed in the basal layer is collagen type XVII alpha 1 chain (COL17A1), which may play a role in hemidesmosome integrity and the attachment of basal keratinocytes to the underlying basement membrane. Another example is keratin 5 (KRT5), a type II cytokeratin which belongs to the keratin family of proteins and is involved in keeping the structural integrity of the basal cells together with keratin 14. Mutations in these types of keratin genes are associated with a complex of diseases termed epidermolysis bullosa simplex.
Epididymal basal cellsBasal epithelial cells that sense luminal contents and signal to principal cells. They aid barrier integrity and epididymal homeostasis. As shown in Table 10, 388 genes show elevated expression in epididymal basal cells compared to other cell types. Basal prostatic cellsBasal prostatic cells play an important part in the structural and luminal integrity of the prostate glands. Disruptions in these cells are associated with cancer-related issues. As shown in Table 10, 104 genes show elevated expression in basal prostatic cells compared to other cell types. An example of a protein with elevated expression in basal prostatic cells is claudin 1 (CLDN1), which as a component of tight junctions enables cell to cell adhesion.
Specialized epithelial cell functionEpithelial cells form sheets of cells, epithelia, that line the outer and inner surfaces of the body and constitute the building blocks for glandular tissues. Hence, epithelial cells are found in many parts of the body, including skin, airways, the digestive tract, glandular tissues and organs, as well as the urinary and reproductive systems. The wide range of functions of epithelial cells can be broadly divided into two main categories, being in charge of the transfer of compounds in or out of the body, as well as being a protective barrier against invading pathogens and physical, chemical or biological abrasion. The histology of organs that contain specialized epithelial cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundHere, the protein-coding genes expressed in specialized epithelial cells are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in different specialized epithelial cell types. The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq and snRNA-seq experiments (36 datasets) covering 34 tissues. All datasets (unfiltered read counts of cells) were clustered independenty using leiden clustering, resulting in a total of 1175 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The RNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding counts per million (nCPM) for all protein-coding genes. A specificity and distribution classification was performed for both single cell types individually, as well as grouped into 53 main cell type groups. The specificity classification determined the number of elevated genes, while the distribution determined whether genes are detected in one, several or all cell types or cell type groups. It should be noted that since the analysis was limited to datasets representing 34 tissue types, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity. Relevant links and publications Uhlén M et al., Tissue-based map of the human proteome. Science (2015) |
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