The existence of multipotent stem cells with epithelial–mesenchymal transition features in the human liver bud

Abstract: During early stage of embryonic development, the liver bud, arising from the foregut endoderm, is the beginning for the formation of future liver three-dimensional structure. While the gene expression profiles associated with this developmental stage have been well explored, the detailed cellular events are not as clear. Epithelial–mesenchymal transition (EMT) was thought to be essential for cell migration in the early vertebrate embryo but seldom demonstrated in human liver development. In this study, we tried to identify the cell populations with both stem cell and EMT features in the human liver bud. Our in situ studies show that the phenotype of EMT occurs at initiation of human liver development, accompanied by up-regulation of EMT associated genes. A human liver bud derived stem cell line (hLBSC) was established, which expressed not only genes specific to both mesenchymal cells and hepatic cells, but also octamer-binding protein 4 (OCT4) and nanog. Placed in appropriate media, hLBSC differentiated into hepatocytes, adipocytes, osteoblast-like cells and neuron-like cells in vitro. When transplanted into severe combined immunodeficiency mice pre-treated by carbon tetrachloride, hLBSC engrafted into the liver parenchyma and proliferated. These data suggests that there are cell populations with stem cell and EMT-like properties in the human liver bud, which may play an important role in the beginning of the spatial structure construction of the liver. [Copyright &y& Elsevier]