Molecular reprogramming of hepatocytes into beta-like cells

The conversion of one differentiated cell-type into another, challenges our long-held view of differentiated cells being in a fixed terminal stage of differentiation, incapable of reversal or change. Such conversions are most favourable between developmentally related cell-types such as hepatocytes from the liver and cells of the pancreas. The main drawback of culturing hepatocytes in vitro has been their limited life span and their rapid de-differentiation in culture. However, the de-differentiation of hepatocytes, and the progressive diminution in the transcription levels of liver-specific genes, is in fact associated with a concomitant induction of a pancreatic gene expression profile.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Liver Specification: A New Role for Wnts in Liver Development

Secreted Wnt proteins control a diverse array of developmental decisions. A recent analysis of the zebrafish mutant prometheus points to a previously unknown role for Wnts during liver specification

Hematopoietic Progenitors from Early Murine Fetal Liver Possess Hepatic Differentiation Potential

Bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes during liver development. It is believed that hepatoblasts originate from endodermal tissue. Here, we provide evidence for the presence of hepatic progenitor cells in the hematopoietic compartment at an early stage of liver development. Flow cytometric analysis showed that at early stages of liver development, approximately 13% of CD45+ cells express Δ-like protein-1, a marker of hepatoblasts. Furthermore, reverse transcriptase-PCR data suggest that many hepatic genes are expressed in these cells. Cell culture experiments confirmed the hepatic differentiation potential of these cells with the loss of the CD45 marker. We observed that both hematopoietic activity in Δ-like protein-1+ cells and hepatic activity in CD45+ cells were high at embryonic day 10.5 and declined thereafter. Clonal analysis revealed that the hematopoietic fraction of fetal liver cells at embryonic day 10.5 gave rise to both hepatic and hematopoietic colonies. The above results suggest a common source of these two functionally distinct cell lineages. In utero transplantation experiments confirmed these results, as green fluorescent protein-expressing CD45+ cells at the same stage of development yielded functional hepatocytes and hematopoietic reconstitution. Since these cells were unable to differentiate into cytokeratin-19-expressing cholangiocytes, we distinguished them from hepatoblasts. This preliminary study provides hope to correct many liver diseases during prenatal development via transplantation of fetal liver hematopoietic cells