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The endocrine cell-specific proteomeThe endocrine cell transcriptomeAdrenal endocrine cellsPituitary endocrine cellsNeuroendocrine cellsPancreatic islet cellsLeydig cellsOther endocrine cellsEndocrine cell functionBackgroundRelevant links and publications Tissues with endocrine cellsIntestinePancreasTestisOvaryThyroid glandParathyroid glandAdrenal glandPituitary gland
Single cell type methods
The endocrine cell-specific proteomeThe human body has a slow and a fast type of systemic signaling system: the endocrine and the nervous system, respectively. The endocrine system communicates through the production and secretion of messenger biomolecules, called hormones, using the cardiovascular system. The cells in charge of the production and secretion of hormones are called endocrine cells and are distributed in many parts of the body in the form of major endocrine organs, such as the adrenal gland and thyroid gland, or organ-associated cells distributed throughout the human body, in for example the brain and the digestive system. Hormones regulate numerous functions of the body, including digestion, reproduction, and fight-and-flight response. Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in endocrine cells and 1391 of these genes show an elevated expression in any endocrine cells compared to other cell type groups. In-depth analysis of the elevated genes in endocrine cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in the following types of endocrine cells: adrenal endocrine cells, pituitary endocrine cells, enteroendocrine cells, pancreatic islet cells, and Leydig cells. The endocrine cell transcriptomeThe scRNA-seq-based endocrine cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific endocrine cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:
Adrenal endocrine cellsThe main function of the adrenal gland is to supply the body with two different sets of hormones, steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. The cortical steroid hormones are involved in metabolic function, electrolyte balance and have androgenic effects. Catecholamines are released in response to stress and their effect is mainly described as the flight-and-fight response. The grouped cell type Adrenal endocrine cells is based on two different cell types: cortical cells and medullar cells, which enables detailed comparison on cell type level. Table 2 shows the number of genes categories as elevated when comparion expression level across all 154. Table 2. Number of genes in the subdivided specificity categoies of elevated expression in the analyzed adrenal endocrine cell types.
Adrenal cortex cellsSteroidogenic cells that synthesize mineralocorticoids, glucocorticoids, and adrenal androgens. These hormones regulate salt balance, stress responses, and metabolism. As shown in Table 2, 377 genes show elevated expression in adrenal cortex cells compared to other cell types.
Adrenal medulla cellsAdrenal medulla cells are hromaffin cells that secrete epinephrine and norepinephrine in response to sympathetic stimulation. They mediate rapid "fight‑or‑flight" cardiovascular and metabolic responses. Several proteins are linked to this process, including dopamine beta-hydroxylase (DBH), an enzyme expressed in the medulla of the adrenal gland. As shown in Table 2, 456 genes show elevated expression in adrenal medulla cells compared to other cell types.
Pituitary endocrine cellsThe pituitary gland, at the base of the brain, is referred to as the master endocrine gland since it regulates most other endocrine organs in the body. The anterior part consists mainly of hormone-producing epithelial cells (somatotropes, corticotrophs, thyrotropes, gonadotropes, and lactotropes) that store hormones in secretory granules. Those hormones are later released into the bloodstream and facilitate further downstream effects in peripheral tissues. Hormones like, follicle-stimulating hormone (FSHB), and luteinizing hormone (LHB), produced in gonadotropes and important regulators of the reproductive system. Table 3. Number of genes in the subdivided specificity categoies of elevated expression in the analyzed endocrine cell types.
CorticotrophsAs shown in Table 3, 485 genes show elevated expression in Corticotrophs compared to other cell types. Anterior pituitary cells that produce adrenocorticotropic hormone (ACTH, also called POMC). ACTH stimulates the adrenal cortex to release glucocorticoids during stress. TBX19 also called T-PIT is a transcription factor crucial for the differentiation of corticotroph cell lineage.
GonadotrophsAs shown in Table 3, 476 genes show elevated expression in Gonadotrophs compared to other cell types. Pituitary cells that secrete luteinizing hormone (LHB) and follicle‑stimulating hormone (FSHB). These hormones regulate gametogenesis and sex steroid production in the gonads. Gonadotropin releasing hormone receptor (GNRHR) and Gonadotroph enriched membrane protein (GEMP also called TGFBR3L) are also two examples of proteins with gonadotroph enriched expression.
LactotrophsAs shown in Table 3, 576 genes show elevated expression in Lactotrophs compared to other cell types. Pituitary cells that synthesize prolactin (PRL). Prolactin promotes mammary gland development and milk production. The function of GPR50 in lacrotroph cells is unknown, which is interesting considering its enriched expression in these cells.
SomatotrophsAs shown in Table 3, 561 genes show elevated expression in Somatotrophs compared to other cell types. Growth hormone‑producing cells of the anterior pituitary. Growth hormone drives somatic growth and regulates metabolism via IGF‑1. Both the growth hormone 1 (GH1) and Growth hormone releasing hormone receptor (GHRHR) show enriched expression in somatotrophs.
ThyrotrophsAs shown in Table 3, 0 genes show elevated expression in Thyrotrophs compared to other cell types Anterior pituitary cells that release thyroid‑stimulating hormone (TSH). TSH stimulates the thyroid gland to produce T3 and T4, controlling basal metabolic rate and development. Thyrotrophs in this dataset lacks genes with cell enriched expression, but share several genes categorised as group enriched and enhanced with other pituitary endocrine cells, such as Thyrotropin releasing hormone receptor (TRHR) expressed by both lactotroph and thyrotroph.
Neuroendocrine cellsEnteroendocrine cells are neuroendocrine cells, hormone‑secreting, scattered throughout the gastrointestinal epithelium. They sense luminal nutrients and release peptides that regulate digestion, appetite, and motility. Table 4. Number of genes in the subdivided specificity categoies of elevated expression in neuroendocrine cell types compared to all other cell types.
An important protein in enteroendocrine and neuroendocrine cells of the gastrointestinal tract is chromogranin A (CHGA), a precursor for several hormones necessary for maintaining balance in e.g. insulin production in the pancreas and adrenaline release in the adrenal gland. CHGA is produced by endocrine cells in several tissues, but its expression is elevated in neuroendocrine cells.
Pancreatic islet cellsThe pancreatic islet cells (also called the islets of Langerhans) are clusters of hormone-producing cells in the pancreas that regulate blood glucose levels. They contain several cell types, including alpha cells, which secrete glucagon to raise blood glucose; beta cells, which secrete insulin to lower blood glucose; delta cells, which produce somatostatin to inhibit both insulin and glucagon release; PP (gamma) cells, which secrete pancreatic polypeptide to help regulate pancreatic secretions; and epsilon cells, which produce ghrelin involved in appetite regulation. Together they maintain blood glucose homeostasis. Table 5. Number of genes in the subdivided specificity categoies of elevated expression in pancreatic islet cell types compared to all other cell types.
As shown in Table 1, 179 genes show elevated expression in pancreatic endocrine cells compared to other grouped cell types, while in Table 5 it shows 328 genes classified as elevated in pancreatic islet cells when comparing all 154 cell types. Examples of proteins expressed in pancreatic endocrine cells include insulin (INS), which is secreted by Beta cells, following elevated blood glucose levels and stimulates glucose uptake upon binding insulin receptors. Another protein with elevated expression is glucagon (GCG) specifically expressed by the alpha cells of the pancreatic islet. The different types of islet cells are separated into different clusters and visible on the cluster detail level, however the specificity category is only calculated based on the endocrine cells as a group.
Leydig cellsLeydig cells are hormone-producing endocrine cells that are located outside the seminiferous ducts in the testis. The interactions between Leydig cells, Sertoli cells, and germinal cells are essential, both for the development of testis and the progress of spermatogenesis. As shown in Table 1, 154 genes show elevated expression in Leydig cells compared to other groupled cell types while in Table 6 it shows 343 genes classified as elevated in Leydig cells when comparing all 154 cell types. Table 6. Number of genes in the subdivided specificity categoies of elevated expression in Leydig cell types compared to all other cell types.
Of the highly enriched genes in testis, only a few are specifically expressed in Leydig cells. An examples of protein with elevated expression in Leydig cells include delta like non-canonical Notch ligand 1 (DLK1) which is known to maintain cells in an undifferentiated state.
Other endocrine cellsThere are additional endocrine cells in the body that currently lack scRNA-seq data at Human Protein Atlas. Endocrine cells are also found in the thyroid gland. The endocrine cells of the thyroid gland are important for the regulation of metabolic rate. They produce the thyroid hormones thyroxine (T4), which is converted to another important hormone triiodothyronine (T3) through the action of enzyme iodotyrosine deiodinase (IYD). Four tiny parathyroid glands are positioned behind the thyroid gland, whose endocrine cells play an important role in the regulation of calcium homeostasis by producing and releasing parathyroid hormone (PTH).
Endocrine cell functionEndocrine cells are characterized by the secretion of various hormones (signaling molecules) to the blood. These hormones are usually transported from their production site to other organs where they regulate numerous functions of the body, including digestion, reproduction, fight-and-flight response, metabolism, sleep, and psychological states. Hormone production is dynamic and feedback loops strictly regulate the amount of hormones depending on numerous factors e.g. circadian clock, age, menstrual cycle, and pregnancy. Hormone production in endocrine cells is stimulated mainly by endocrine signaling or neuroendocrine signaling, depending on the characteristics of the target endocrine cell. During endocrine signaling, hormones produced by other endocrine cells bind to receptors on the surface of the target endocrine cells and set off an intracellular signaling cascade that results in the production and secretion of the appropriate hormone. An example of this is the so-called hypothalamus - pituitary - gonadal axis, which involves the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which bind to gonadotropic cells in the anterior part of the pituitary gland. In response, gonadotropic cells release follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which control gonadal function in reproductive organs. Neuroendocrine signaling is restricted to neuroendocrine cells since they share characteristics of both neuronal and endocrine cells. They produce hormones in response to nervous stimuli (changes in membrane potential). Examples are enteroendocrine cells, cells in the adrenal medulla, and pancreatic endocrine cells. The histology of organs that contain endocrine cells, including interactive images, is described in the Protein Atlas Histology Dictionary. BackgroundHere, the protein-coding genes expressed in endocrine 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 endocrine 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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