The Stathmin 1-lineage Contributes to Acinar Regeneration but Not to Neoplasia Upon Oncogenic Kras Expression

BACKGROUND & AIMS: expression. METHODS: expression. RESULTS: The Stmn1-lineage contributes to baseline acinar cell turnover under physiological conditions. Furthermore, these cells rapidly proliferate and repopulate the acinar compartment in response to acute injury in an acinar-to-ductal metaplasia (ADM)-independent manner. Moreover, acinar regeneration during chronic pancreatitis progression is in conjunction with a decline in the proliferative capacity of the Stmn1-lineage. Interestingly, newly generated acinar cells display increased susceptibility to additional injury during recurrent acute pancreatitis. Finally, given their inability to form ADMs, the Stmn1-lineage fails to form pancreatic intraepithelial neoplasia upon oncogenic Kras expression. CONCLUSIONS: Our findings establish the Stmn1-lineage as a pivotal subpopulation for acinar regeneration. The ability of these cells to restore acinar tissue in an ADM-independent manner distinguishes them as a critical regenerative population. This study presents a new paradigm for acinar regeneration and repair in the context of pancreatitis and neoplasia.