Acinar tissue plasticity has been demonstrated in many pancreatic diseases.And the appearance of hepatic foci in adult pancreatic tissue is one example of metaplastic transformation which was well documented in animal experiments and in cases of pancreatic cancer patients.Our previous studies indicate pancreatic hepatocytes were possibly directly derived from acinar cell transdifferentiation with involvement of CCAAT enhancer binding proteins (C/EBPs).However,the molecular basis of the cell plasticity remains to be defined.In the present study,we revealed that an intermediate cell type expressing ATP binding cassette transporter G2 (ABCG2) was generated in the early phase of hepatic conversion.On further characterization of ABCG2-expressing intermediate cells,we found these cells expressed pancreatic stem/progenitor marker-Nestin and displayed side-population (SP) phenotype,the capacity to efflux fluorescent Hoechst 33342 dye which has been recognized as a common feature of somatic stem cells.Treatment of these SP-isolated intermediate cells with Dexamethasone,Oncostatin M,Tumor growth factor a or Glucagon-like peptide one,cells can either mostly differentiate into hepatocyte-like cells,ductal cells or insulin-producing endocrine cells suggesting ABCG2-expressing SP cells were possibly multipotent stem/progenitor cells.Furthermore,activation of PI3K/Akt signaling pathway was found to involve in regulating the generation of SP phenotype and in hepatic transdifferentiation.