Using flowcytometry combined with single-cell-based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability in the developing mouse liver. c-Met+ CD49f+/low CD29+ c-Kit- CD45- TER119- cells in fetal liver could be clonally propagated in culture, where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes, with reconstitution of hepatic cord and bile duct structures. These data indicate that self-renewing multipotent stem cells are retained in midgestational developing liver. The pancreas also contains a population of pancreatic stem cells that generate endocrine, exocrine, and ductal cells during development, neogenesis, and regeneration. By combining flowcytometry and clonal analysis, we show here that stem/progenitor cells of pancreatic endocrine and exocrine cells that reside in the neonatal mouse pancreas. Clonally isolated stem/progenitor cells could be used to reveal the mechanism of cell differentiation in digestive organs, and also could provide new insight into therapies for liver diseases, diabetes mellitus and cancer. [J Physiol Sci. 2006;56 Suppl:S3]