Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation.

摘要: Understanding the biological potential of fetal stem/progenitor cells will help define mechanisms in liver development and homeostasis. We isolated epithelial human established phenotype-specific changes gene expression during continuous culture conditions. Fetal displayed stem cell properties with multilineage expression, extensive proliferation generation mesenchymal lineage cells, although initial phenotype was rapidly supplanted by mesoendodermal culture. This meso-endodermal genetically regulated through cytokine signaling, including transforming growth factor β, bone morphogenetic protein, fibroblast other signaling pathways. Reactivation HNF3α (FOXA1) transcription factor, a driver hepatic specification primitive endoderm, indicated that represented an earlier developmental stage cells. found formed mature hepatocytes vivo, after genetic manipulation using lentiviral vectors, offering convenient assays for analysis further differentiation fate. Taken together, these studies demonstrate plasticity offer paradigms defining regulating switching provide avenues phenotypes applications such as therapy.