The pancreas is a combined endocrine and exocrine gland t...

The pancreas is a combined endocrine and exocrine gland that develops from an outgrowth of the primitive foregut and is closely associated with the upper duodenum (Liggitt and Dintzis, “Pancreas”, pp. 241-250). The exocrine pancreas, which comprises more than 95% of the pancreas mass, consists of lobules formed by tubuloacinar glands that are built by two main cell types: acinar cells, which synthesize and secrete digestive enzymes, and ductal cells, which line the ducts extending throughout the pancreas to the duodenum. A third cell type, centroacinar cells, is rare and has been characterized in mouse, but human studies have been inconclusive (Liggitt and Dintzis, “Pancreas”, pp. 241-250). The majority of single-cell omics data is restricted to pancreatic Langerhans islet cells due to difficulties in maintaining the integrity of ductal and acinar cells during pancreas dissociation (reviewed in Alvarez Fallas et al. 2021).

During embryonic development, primary multipotent pancreatic progenitor cells (MPCs) that originate from the definitive endoderm-derived foregut endoderm, form ventral and dorsal pancreatic buds (reviewed in Jennings et al. 2015, Tritschler et al. 2017, Alvarez Fallas et al. 2021). All adult pancreatic cell types are derived from the MPCs (Tritschler et al. 2017, Alvarez Fallas et al. 2021).

Acinar cells are large pyramidal secretory epithelial cells that surround the lumen, thus forming an acinus (Liggitt and Dintzis, “Pancreas”, pp. 241-250). Acinar cells have prominent endoplasmic reticulum and Golgi networks, and their cytoplasm contains a large number of secretory zymogen granules, filled with different digestive enzymes, that are clustered in the vicinity of the apical surface (Liggitt and Dintzis, “Pancreas”, pp. 241-250). At the surface of the lumen, acinar cells are attached by apical tight junctions, while their basal surface is associated with the basal lamina (Liggitt and Dintzis, “Pancreas”, pp. 241-250). Centroacinar cells, characterized in rodents, are clear-staining spindle-shaped cells continuous with the lumen of intercalated pancreatic ducts (Liggitt and Dintzis, “Pancreas”, pp. 241-250).

Ductal epithelial cells line the pancreatic ducts in a single layer, changing the shape as ducts increase in size from cuboidal, through low columnar, to high columnar epithelium (Liggitt and Dintzis, “Pancreas”, pp. 241-250). Ductal epithelial cells may have cilia or microvilli on their apical surface (Liggitt and Dintzis, “Pancreas”, pp. 241-250). Besides ductal epithelial cells, main pancreatic ducts sometimes include goblet cells (Liggitt and Dintzis, “Pancreas”, pp. 241-250).

Either acinar or ductal cells are thought to give rise to pancreatic ductal adenocarcinoma (PDAC) (reviewed in Alvarez Fallas et al. 2021). Ductal cell-derived PDAC is thought to be more aggressive and is characterized by activating KRAS mutations and loss-of-function of TP53, FBXW7 or PTEN (reviewed in Alvarez Fallas et al. 2021). Acinar cell-derived PDAC is thought to have a slower progression, and to frequently present as pancreatic intraepithelial neoplasia (reviewed in Alvarez Fallas et al. 2021).