Stem cell is the term used to describe those undifferentiated cells that are capable of both self-renewal and giving rise to specialized functional cells. Stem cells are of pivotal importance for organ and tissue integrity and for injury and disease repair. Based on their developmental potential, stem cells are classified into four categories: (1) totipotent, (2) pluripotent, (3) multipotent, and (4) oligopotent/unipotent. Totipotent stem cells give rise to all three germ layers and extraembryonic tissues. Pluripotent stem cells are capable of generating the embryo proper, comprising all organs with ectoderm, mesoderm, and endoderm origins. Multipotent stem cells differentiate only into tissue-specific progenitors of a given organ. Unipotent or oligopotent stem/progenitor cells give rise only to one or a few functional cell types. Depending on the developmental stages of their origin, stem cells are known as embryonic stem cells (ESCs, generated from isolated inner cell mass of preimplanted embryos); epiblast stem cells (generated from postimplanted epiblast-stage embryos); germline-derived stem cells (generated from embryonic gonadal ridges or postnatal testes); induced pluripotent stem cells (iPSCs, originally induced from fetal or adult cells by the overexpression of defined transcription factors) or tissue-specific stem cells (derived from postnatal tissues).
A group of special cells in the thickened DE epithelium at E9.0–9.5 along the dorsal and ventral surfaces of the posterior mouse foregut expresses the gene named Pdx1 (pancreas and duodenum homeobox 1). Pdx1 is a member of the parahox homeobox transcription factor family and is essential for both the expansion of pancreas primordial populations and the function of adult β cells.
Genetic lineage tracing experiments demonstrated that Pdx1-expressing (Pdx1+) cells give rise to duct, acinar, and endocrine tissues in the pancreas. These progenitors are located at the tip of the branching pancreatic tree marked by Pdx1+Ptf1a+(pancreas transcription factor 1a) Cpa1+(carboxypeptidase 1). The Pdx1+ cells are able to take up bromodeoxyuridine, a thymidine analogue incorporated into DNA during S-phase of the cell cycle, indicating that these cells are proliferative. We previously developed protocols for dissociated fetal pancreatic cells committed from Pdx1+ progenitors to generate cystic epithelial colonies containing β cells in the presence of laminin 1,1,1 and growth factors. Recently, lineage tracing demonstrated that the expandable cystic epithelial colonies are only generated from Pdx1+ progenitor-derived Sox9+ cells. Future studies are required to determine whether all cystic epithelial colonies stochastically commit to various lineages or only certain fractions of cystic epithelial colony cells have defined differentiation potential.