The pancreas secretes enzymes that are required for the digestion of food in the intestine. Two main pancreatic cell types are involved in this — acinar cells, which secrete these enzymes, and ductal cells, which line channels to the intestine. The most common type of pancreatic cancer arises in a form that recapitulates such pancreatic ducts, both in its gland-like structure and in its pattern of protein expression. Yet, despite this similarity, substantial uncertainty remains regarding the cell type (cell of origin) that gives rise to pancreatic cancer.
Working in mice, the authors focused on a particular subset of acinar cells — those expressing the enzyme telomerase reverse transcriptase (Tert). This enzyme enables dividing cells to maintain the lengths of structures at their chromosome ends called telomeres by facilitating the reaction that adds nucleotides to these chromosomal tips. The shortening of telomeres results in the activation of Tert to maintain telomere length and thereby avoid catastrophic genomic damage. Technical challenges have previously limited the options available to visualize the expression of Tert in cells, so Neuhöfer and colleagues used genetically engineered mice in which cells that express Tert are labelled by the expression of a fluorescent protein. This system allowed the authors to determine the prevalence of Tert expression in different populations of cells in the pancreas, and to assess the cellular lineages arising from Tert-expressing cells.
Neuhöfer and colleagues discovered that acinar and not ductal cells expressed Tert (Fig. 1). The authors also generated mice with acinar cells that were randomly labelled irrespective of their Tert-expression status. Only the Tert-expressing acinar cells formed ‘expanded clones’ — groups of cells arising from single parental cells. This was true both with increasing age and acutely, in response to injury in the form of chemically induced pancreatic inflammation.
