Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis

Abstract

A central question in stem cell biology is whether organ homeostasis is maintained in adult organs through undifferentiated stem cells or self-duplication of specialized cell populations. To address this issue in the exocrine pancreas we analyzed the Bmi1-labeled cell lineage of pancreatic acinar cells. Previously, we had shown that inducible linage tracing with BmM-Cre-estrogen receptor (ER) in the small intestine specifically, labels "classical" undifferentiated intestinal stem cells. In this article we demonstrate that the Bmi1-Cre-ER system labels a subpopulation of differentiated acinar cells in the exocrine pancreas whose derivatives are still present, at a steady-state level, 1 year after a single TM pulse. This study suggests that Bmi1 is a marker for a subpopulation of self-renewing acinar cells, indicating that self-renewal is not an exclusive feature of adult undifferentiated stem cells. Further, the extended period that Bmi1-labeled acinar cells retain a pulse of BrdU suggests that some of this subpopulation of cells are not continuously replicating, but rather are set aside until needed. This cellular behavior is again reminiscent of behavior normally associated with more classical adult stem cells. Setting aside cells capable of self-renewal until needed retains the advantage of protecting this subpopulation of cells from DNA damage induced during replication.