The glandular epithelial cell-specific proteomeGlandular epithelial cells are multifunctional cells with the main functions of secretion and absorption. Glandular epithelia are found at the surface of inner cavities of the respiratory system, gastrointestinal tract, uterus and fallopian tube, and glandular organs such as pancreas, prostate and breast. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in glandular epithelial cells and 2202 of these genes show an elevated expression in any glandular epithelial cells compared to other cell type groups. In-depth analysis of the elevated genes in glandular epithelial cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in Acinar cells, gastroc glandular cells, eneterocytes, goblet cells, glandular cells of endometrium, esophagus, lung and prostate, secretory cells of breast, endometrium, fallopian tube and lung as well as luminal cells in breast and endometrium. The glandular epithelial cell transcriptomeThe scRNA-seq-based glandular epithelial cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific glandular epithelial cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
Acinar cellsAcinar cells are specialized secretory cells that produce and release enzymes or proteins essential for digestion and lubrication. Found in the ocular, salivary, and pancreatic glands, they secrete tear components, saliva, and digestive enzymes, respectively, supporting both protective and digestive functions. Table 2. Number of genes in the subdivided specificity categories of elevated expression in the analyzed acinar cell types.
Lacrimal acinar cellsSecretory cells of lacrimal and related ocular glands that produce the aqueous layer of the tear film. Their protein‑rich secretions lubricate and protect the ocular surface. As shown in Table 2, 189 genes show elevated expression in lacrimal acinar cells compared to other cell types
Salivary acinar cellsSerous glandular cells produce a watery secretion containing antimicrobial proteins as well as enzymes to initiate digestion. As shown in Table 2, 259 genes show elevated expression in salivary acinar cells compared to other cell types. An example of a gene with enriched expression in serous glandular cells is lactoperoxidase (LPO) which is an enzyme that activates antimicrobial agents in the saliva.
Pancreatic acinar cellsExocrine glandular cells are the major cell type in the pancreas. These cells secrete digestive enzymes and NaHCO3 into ducts leading to the duodenum. As shown in Table 2, 327 genes show elevated expression in pancreatic acinar cells compared to other cell types An examples of exocrine glandular cell specific gene is a Ca2+ dependent phospholipase and carboxypeptidase A1 precursor (CPA1), which is a protease that cleaves C-terminally branched-chain and aromatic amino acids.
Gastric glandular cellsGastric glandular cells coordinate the secretion of mucus, enzymes, and acid essential for digestion and protection of the stomach lining. Foveolar and mucous neck cells produce protective mucus, parietal cells secrete hydrochloric acid for digestion, and chief cells release pepsinogen to initiate protein breakdown. Table 3. Number of genes in the subdivided specificity categories of elevated expression in the analyzed gastric glandular cell types.
Foveolar cellsSurface mucous cells of the stomach that secrete bicarbonate‑rich mucus. They protect the gastric epithelium from acid and pepsin. As shown in Table 3, 452 genes show elevated expression in foveolar cells compared to other cell types. An example of a protein with elevated expression in foveolar cells is trefoil factor 1 (TFF1). Both are present in the mucus gel covering the epithelium and protect the mucosa from damage.
Mucous neck cellsMucus‑secreting cells located in gastric glands that also act as progenitors. They help protect and renew the gastric epithelium. As shown in Table 3, 192 genes show elevated expression in mucous neck cells compared to other cell types.
Parietal cellsAcid‑secreting gastric cells that produce hydrochloric acid and intrinsic factor. They are essential for protein digestion and vitamin B12 absorption. As shown in Table 3, 545 genes show elevated expression in parietal cells compared to other cell types. Gastric parietal cells produce hydrochloric acid with the help of ion transport proteins, such as ATPase H+/K+ transporting beta subunit (ATP4B), which is key for digestion of proteins.
Gastric chief cellsGastric gland cells that secrete pepsinogen and gastric lipase. They contribute to protein and fat digestion in the stomach. As shown in Table 3, 332 genes show elevated expression in gastric chief cells compared to other cell types. EnterocytesEnterocytes, including colonocytes, are the primary absorptive cells of the intestinal epithelium responsible for nutrient, water, and electrolyte uptake. They also contribute to barrier function and immune defense, maintaining intestinal homeostasis and protecting against microbial invasion. Table 4. Number of genes in the subdivided specificity categories of elevated expression in enterocytes and colonocytes.
EnterocytesEnterocytes are brush‑border epithelial cells of the small intestine that absorb nutrients, water, and electrolytes. They express transporters and enzymes for digestion and uptake. As shown in Table 4, 921 genes show elevated expression in enterocytes compared to other cell types. An example of a protein with elevated expression in enterocytes is intestinal alkaline phosphatase (ALPI) that has an important role in maintaining a healthy gut microbiome.
ColonocytesAbsorptive epithelial cells of the colon and rectum that reclaim water and electrolytes. They also metabolize short‑chain fatty acids produced by gut microbes. As shown in Table 4, 659 genes show elevated expression in colonocytes compared to other cell types. An example is membrane spanning 4-domains A12 (MS4A12), which is a membrane receptor involved in cell proliferation and motility.
Glandular cellsGlandular cells are specialized epithelial cells that produce and secrete a variety of substances vital for tissue function and homeostasis. In organs such as the submucosa, prostate, and endometrium, these cells secrete mucus, proteins, and signaling molecules that aid in lubrication, protection, and reproductive or immune regulation. Table 5. Number of genes in the subdivided specificity categories of elevated expression in respective glandular cell types.
Submucosal glandular cellsSecretory cells in submucosal glands of the airway and GI tract. They produce mucus and serous fluids that protect and lubricate mucosal surfaces. As shown in Table 5, 84 genes show elevated expression in Submucosal glandular cells compared to other cell types. An example of a protein with elevated expression in submucosal glandulare cells is SLPI.
Prostatic glandular cellsThe prostate is composed of prostatic glands and a non-glandular stroma. Within the glandular structures, there are secretory cells, which are separated from the basement membrane and stroma by a layer of basal cells. As shown in Table 5, 331 genes show elevated expression in prostatic glandular cells compared to other cell types. One example of proteins with elevated expression in prostatic glandular cells is kallikrein related peptidase 3 (KLK3), generally referred to as prostate-specific antigen (PSA), a serine protease that is synthesized by glandular cells of the prostate. Under normal conditions, PSA is secreted into the extracellular fluid in small quantities and its function is believed to be important for the liquefaction of seminal fluid in the seminal coagulum and to allow sperm to swim freely. Transglutaminase 4 (TGM4) is an enzyme assoicated with the reproductive process with the ability to cross-link proteins and conjugate polyamines to specific proteins in the seminal tract.
Prostatic club cellsNon‑ciliated secretory cells in the prostate analogous to airway club cells. They secrete protective proteins and may serve progenitor roles. As shown in Table 5, 167 genes show elevated expression in Prostatic club cells compared to other cell types.
Endometrial glandular cellsSecretory cells that line uterine glands and produce factors that support implantation. Their activity varies across the menstrual cycle under hormonal control. During the proliferative phase of the menstrual cycle, endometrial glands, stroma and vascular endothelium all proliferate leading to an increased volume of the endometrium. The glands are lined by mucus-producing glandular cells with interspersed ciliated cells, and luminal cells line the epithelium outside of the glands. As shown in Table 5, 458 genes show elevated expression in Endometrial glandular cells compared to other cell types. An example of a protein with elevated expression in endometrial glandularl cells is progestagen associated endometrial protein (PAEP), which is a glycoprotein expressed in glandular cells with an essential role in regulating uterine environment suitable for pregnancy.
Goblet cellsGoblet cells are specialized secretory epithelial cells that produce and release mucins to form a protective mucus layer over mucosal surfaces. Found in the conjunctiva and intestinal epithelium, they maintain lubrication, trap pathogens, and support barrier integrity to protect underlying tissues. Table 6. Number of genes in the subdivided specificity categories of elevated expression in respective goblet cell types.
Conjunctival goblet cellsMucin‑secreting cells of the conjunctiva that contribute to the tear film. They lubricate the ocular surface and protect against pathogens. As shown in Table 6, 218 genes show elevated expression in conjunctival goblet cells compared to other cell types. Goblet cellsIntestinal goblet cells lay interspersed between the enterocytes in the small intestine and in larger quantities in the large intestine. These cells secrete glycoprotein-rich mucins to create a protective mucus layer over the intestinal epithelia. As shown in Table 6, 419 genes show elevated expression in goblet cells compared to other cell types. An example of a protein with elevated expression in intestinal goblet cells is mucin 2 (MUC2), which is one type of the aforementioned mucin. Another example is chloride channel accessory 1 (CLCA1), which is speculated to be involved in regulation of mucus production and secretion.
Secretory cellsSecretory cells synthesize and release diverse bioactive substances that support tissue function, protection, and communication. Found in the respiratory tract, breast, fallopian tube, and endometrium, these cells produce mucus, milk, and reproductive secretions essential for lubrication, nourishment, and defense. Table 7. Number of genes in the subdivided specificity categories of elevated expression in respective secretory cell types.
Respiratory secretory cellsAirway epithelial cells (club/secretory) that produce components of mucus and host‑defense proteins. They detoxify inhaled substances and contribute to epithelial repair. As shown in Table 7, 183 genes show elevated expression in respiratory secretory cells compared to other cell types.
Breast secretory cellsBreast glandular cells comprise the mammary gland, which can either be lactating or non-lactating. During pregnancy, non-lactating mammary glands undergo morphological alterations and begin to produce milk due to the influence of hormonal changes. As shown in Table 7, 170 genes show elevated expression in breast secretory cells compared to other cell types.
Breast lactating cellsHighly active mammary epithelial cells producing milk lipids, proteins, and lactose. They respond to prolactin and oxytocin to sustain lactation. As shown in Table 7, 412 genes show elevated expression in breast lactating cells compared to other cell types.An example of a protein with elevated expression in breast glandular cells is lactalbumin alpha (LALBA), a key enzyme in milk production.
Fallopian secretory cellsThe glandular epithelium of the fallopian tube is lined by mucus-producing secretory cells and ciliated cells, working in tandem to secrete and move mucus in order to transport the gamets during sexual reproduction. They shape the microenvironment for fertilization and transport. As shown in Table 7, 139 genes show elevated expression in fallopian secretory cells compared to other cell types. An example of a protein with elevated expression in secretory cells is oviductal glycoprotein 1 (OVGP1), which is a glycoprotein expressed by the secretory cells during the late follicular phase of the ovarian cycle.
Endometrial secretory cellsEndometrial secretory cells are epithelial cells that, in the luteal phase, secrete glycogen and factors that favor implantation. They help create a receptive endometrium. As shown in Table 7, 258 genes show elevated expression in endometrial secretory cells compared to other cell types. Luminal cellsLuminal cells line the inner surfaces of glandular tissues and play key roles in secretion, absorption, and hormonal responsiveness. In the breast and endometrium, these hormone-responsive cells regulate tissue remodeling, secretion, and functional changes during reproductive and hormonal cycles. Table 8. Number of genes in the subdivided specificity categories of elevated expression in respective luminal cell types.
Breast hormone-responsive cellsMammary luminal cells expressing estrogen and progesterone receptors. They sense systemic hormones to regulate growth and differentiation of the gland. As shown in Table 8, 131 genes show elevated expression in breast hormone-responsive cells compared to other cell types.
Endometrial luminal cellsSurface epithelial cells lining the uterine cavity that interact directly with the embryo. They mediate adhesion and initiate implantation signaling. As shown in Table 8, 400 genes show elevated expression in endometrial luminal cells compared to other cell types. Glandular 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. Transfer of compounds is a key process for glandular epithelial cells involved in absorption and secretion. The epithelial cells in the digestive system form vast surfaces to enable efficient absorption of the ingested food particles. The same food particles must be predigested into smaller constituents before they can be taken up by the absorptive epithelial cells, a process that is made possible by the secretion of compounds such as enzymes and acid. Mucus secretion is also another important secretory function of glandular epithelial cells that protect the epithelia and enable efficient transport of microorganisms, gametes, particles, and smaller compounds in different areas of the body, such as the airways, the digestive system, and the reproductive system. The histology of organs that contain glandular epithelial cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundHere, the protein-coding genes expressed in glandular 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 glandular 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) |