Abstract
In the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.
Highlights
In the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear
A small population of green fluorescent protein (GFP)+ cells were observed in the acinar, duct and islet compartments that were considered to be S ETD4+ cells, while as a control, no recombinant GFP was detected in the absence of TAM-induction and in wide type mice (Fig. 1b, S1b)
Some investigators support the concept of pancreatic plasticity, that pancreatic exocrine cells can trans-differentiate to a progenitor-like cell in response to injury[2,3,5,7]
Summary
The presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. The current explanation for the regenerative capacities of the exocrine pancreas is that acinar cells in the adult pancreas show a high degree of plasticity and can undergo trans-differentiation to a progenitorlike cell type with ductal c haracteristics[7,8,9] This process is considered an important feature facilitating pancreatic regeneration after injury. Previous studies in various types of tissues have identified that these quiescent cells can contribute to the long-term maintenance of a stem cell pool by preserving proliferation capacity and acting as a cell reservoir They facilitate tissue homeostasis and regeneration in response to tissue injury upon activation[41,42]. Our results reveal that S ETD4+ cells make a significant contribution to pancreatic development and response to pancreatic injury in adults
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