The pancreas cell type enriched transcriptome
The pancreas is a composite organ with both exocrine and endocrine functions. The exocrine compartment includes glandular and ductal cells that secrete enzymes into the early portion of the gastrointestinal tract to assist digestion of food. The endocrine function of the pancreas is driven by alpha and beta cells within the islets of Langerhans, which secrete hormones that are important in the regulation of blood glucose levels.
828 genes were predicted to have cell type specificity in the pancreas.
Pancreas cell type enriched transcriptome: Summary
Genes with predicted cell type specificity within pancreas are detailed in the Table 1. Identified cell type enriched 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):
NB: Genes co-enriched in alpha and beta cells appear in both categories.
Pancreas cell type enriched transcriptome: Illustrative examples
In-depth analysis of the enriched genes in pancreas cell types using antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in different pancreas cell types including the alpha and beta cells within islets of Langerhans, exocrine glands and ducts.
Proteins specifically expressed in islets of Langerhans
The islet cells constitute 1-2% of the pancreas and are responsible for maintaining a steady blood glucose level by secreting hormones regulating uptake and release of glucose.
The primary function of alpha cells is to detect low glucose levels in the blood, and respond by secreting glucagon (GCG) into the blood plasma, which causes release of glucose from glycogen storage located in the liver and other tissues. Alpha cells also produce other plasma proteins, including transthyretin (TTR), a primary transport protein for thyroxine and retinol (vitamin A).
Beta cells act in opposition to Alpha cells, and upon detecting elevated blood glucose levels respond by secreting several hormones, including insulin (INS), which acts to increase the uptake of glucose by cells around the body, especially in the liver and muscle tissue, and stimulate its conversion to glycogen or lipids for storage. Another gene with specificity in alpha cells is synuclein beta (SNCB), whose precise function is unknown.
Alpha and Beta cells
Alpha and beta cells are both endocrine cell types that share a large number of enriched genes. Gene classified as having specificity in both alpha and beta cells include Solute Carrier Family 30 Member 8 (SLC30A8), which is an islet zinc transporter, Secretogranin V (SLC30A8), which is a secreted chaperone protein that prevents the aggregation of other secreted proteins and NK6 Homeobox 1 (PAX6), a transcription factor involved in developmental regulation.
Exocrine glandular cells
The exocrine glandular cells, or acinar cells, of the pancreas produce digestive enzymes that are secreted into the duodenum of the small intestine. Examples of digestive enzymes classified as having specificity in exocrine glandular cells include Amylase alpha 2A (AMY2A), which helps digest long polysaccharides such as starch, while non-enzyme proteins with specificity in exocrine glandular cells include Carboxypeptidase A1 (CPA1), which is involved in inhibiting early activation of the secreted proenzymes, and the endoplasmic reticulum protein 27 (ERP27), which may assist in chaperoning unfolded proteins.
Ductal cells are epithelial cells that line the pancreatic ducts, which transport the digestive enzymes secreted by the glandular cells to the duodenum. Ductal cells themselves secrete bicarbonate into the pancreatic juices, which neutralizes stomach acid and helps regulate the pH of the gastrointestinal tract. Genes classified as having specificity in pancreatic ductal cells include keratin 7 (KRT7), an intermediate filament protein often found in epithelial cells, and the calcium signaling surface receptor Tumor associated calcium signal transducer 2 (TACSTD2).