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Liver development, regeneration, and carcinogenesis.

Kung JW, Currie IS, Forbes SJ, Ross JA - J. Biomed. Biotechnol. (2010)

Bottom Line: As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved.In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches.Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

View Article: PubMed Central - PubMed

Affiliation: Tissue Injury and Repair Group, Medical Research Council Centre for Regenerative Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK. janetkung@gmail.com

ABSTRACT
The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

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Related in: MedlinePlus

The lineage of the developing liver in vivo. Pluripotent embryonic stem (ES) cells from the blastocyst inner cell mass give rise to three principal germ layers: ectoderm, mesoderm, and endoderm. The anterior region of the endoderm will form the foregut. Following hepatic specification of foregut endoderm, hepatic cells (now called hepatoblasts) will bud into the septum transversum and continue to proliferate and differentiate. Maturation into hepatocytes and bile epithelial cells continue until several weeks after birth. The red bars highlight the key stages of liver development. The black bars in the middle are mouse embryos at different stages of development, and the blue bars at the bottom indicate the equivalent stages in human development.
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fig1: The lineage of the developing liver in vivo. Pluripotent embryonic stem (ES) cells from the blastocyst inner cell mass give rise to three principal germ layers: ectoderm, mesoderm, and endoderm. The anterior region of the endoderm will form the foregut. Following hepatic specification of foregut endoderm, hepatic cells (now called hepatoblasts) will bud into the septum transversum and continue to proliferate and differentiate. Maturation into hepatocytes and bile epithelial cells continue until several weeks after birth. The red bars highlight the key stages of liver development. The black bars in the middle are mouse embryos at different stages of development, and the blue bars at the bottom indicate the equivalent stages in human development.

Mentions: Hepatoblasts in the liver bud express serum protein genes specific to hepatocytes such as albumin (alb), transthyretin (ttr), and α-fetoprotein (afp) [30, 31]. These cells are bipotential and soon after mesenchyme invasion differentiate into hepatocytes (α-fetoprotein+/albumin+) and cholangiocytes (cytokeratin (CK)-19+) [5, 32]. The proper balance in the numbers of hepatocytes and cholangiocytes from hepatoblasts is achieved by integrated signalling and transcriptional networks. The Jagged-Notch pathway controls differentiation of hepatoblasts towards a biliary epithelial phenotype [33, 34], while HGF antagonises biliary differentiation and in conjunction with oncostatin M (OSM) promotes hepatocyte differentiation [35]. Following lineage segregation, the percentage of bipotent cells is markedly reduced and most cells are unipotent and irreversibly committed to either the hepatocytic or cholangiocytic lineage. Committed cells exhibit progressive change in morphology and physiologic functions, and this maturation process extends until several weeks after birth as demonstrated by a number of gene array analyses in rodent liver development [36–38]. An overview of embryonic liver development is presented in Figure 1.


Liver development, regeneration, and carcinogenesis.

Kung JW, Currie IS, Forbes SJ, Ross JA - J. Biomed. Biotechnol. (2010)

The lineage of the developing liver in vivo. Pluripotent embryonic stem (ES) cells from the blastocyst inner cell mass give rise to three principal germ layers: ectoderm, mesoderm, and endoderm. The anterior region of the endoderm will form the foregut. Following hepatic specification of foregut endoderm, hepatic cells (now called hepatoblasts) will bud into the septum transversum and continue to proliferate and differentiate. Maturation into hepatocytes and bile epithelial cells continue until several weeks after birth. The red bars highlight the key stages of liver development. The black bars in the middle are mouse embryos at different stages of development, and the blue bars at the bottom indicate the equivalent stages in human development.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821627&req=5

fig1: The lineage of the developing liver in vivo. Pluripotent embryonic stem (ES) cells from the blastocyst inner cell mass give rise to three principal germ layers: ectoderm, mesoderm, and endoderm. The anterior region of the endoderm will form the foregut. Following hepatic specification of foregut endoderm, hepatic cells (now called hepatoblasts) will bud into the septum transversum and continue to proliferate and differentiate. Maturation into hepatocytes and bile epithelial cells continue until several weeks after birth. The red bars highlight the key stages of liver development. The black bars in the middle are mouse embryos at different stages of development, and the blue bars at the bottom indicate the equivalent stages in human development.
Mentions: Hepatoblasts in the liver bud express serum protein genes specific to hepatocytes such as albumin (alb), transthyretin (ttr), and α-fetoprotein (afp) [30, 31]. These cells are bipotential and soon after mesenchyme invasion differentiate into hepatocytes (α-fetoprotein+/albumin+) and cholangiocytes (cytokeratin (CK)-19+) [5, 32]. The proper balance in the numbers of hepatocytes and cholangiocytes from hepatoblasts is achieved by integrated signalling and transcriptional networks. The Jagged-Notch pathway controls differentiation of hepatoblasts towards a biliary epithelial phenotype [33, 34], while HGF antagonises biliary differentiation and in conjunction with oncostatin M (OSM) promotes hepatocyte differentiation [35]. Following lineage segregation, the percentage of bipotent cells is markedly reduced and most cells are unipotent and irreversibly committed to either the hepatocytic or cholangiocytic lineage. Committed cells exhibit progressive change in morphology and physiologic functions, and this maturation process extends until several weeks after birth as demonstrated by a number of gene array analyses in rodent liver development [36–38]. An overview of embryonic liver development is presented in Figure 1.

Bottom Line: As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved.In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches.Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

View Article: PubMed Central - PubMed

Affiliation: Tissue Injury and Repair Group, Medical Research Council Centre for Regenerative Medicine, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK. janetkung@gmail.com

ABSTRACT
The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

Show MeSH
Related in: MedlinePlus