TY - JOUR
T1 - Artificial induction and disease-related conversion of the hepatic fate
AU - Suzuki, Atsushi
N1 - Funding Information:
Our work was generally supported in part by the Program for Improvement of the Research Environment for Young Researchers from the Special Coordination Funds for Promoting Science and Technology commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan , Grants-in-Aid for Scientific Research from the MEXT of Japan, a Health Labour Sciences Research Grant in Japan, the Precursory Research for Embryonic Science and Technology Program of the Japan Science and Technology Agency, and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency. The experiments were approved by the Kyushu University Animal Experiment Committee, and the care of the animals was in accordance with institutional guidelines.
PY - 2013/10
Y1 - 2013/10
N2 - Under normal physiological conditions, the fates of cells that compose various parts of organs are determined during development, and never change to those of other cell types. However, recent advances in induction of cellular reprogramming provide chances to generate a completely different cell type from an original cell source by artificially modulating the microenvironments or gene expressions pattern of cells. Although hepatocytes normally only reside in the liver, the hepatic program can be induced in skin-derived fibroblasts by expressing defined extrinsic transcription factors. These induced hepatocyte-like cells have hepatocyte-specific properties and functionally restore damaged hepatic tissues after transplantation. On the other hand, hepatocytes themselves can be converted into biliary lineage cells as a causative factor of hepatic diseases. Thus, blockade of such disease-related reprogramming of the hepatic fate will become a new therapeutic strategy for refractory diseases in the liver. Moreover, hepatocytes could partially accept the pancreatic program by expressing transcription factors required for pancreas development, suggesting that insulin-producing cells could be generated from hepatocytes and used to treat diabetes. The above-mentioned progress will stimulate studies on the molecular nature of cellular identity and plasticity in hepatocytes, and contribute to the development of potential therapies for liver diseases.
AB - Under normal physiological conditions, the fates of cells that compose various parts of organs are determined during development, and never change to those of other cell types. However, recent advances in induction of cellular reprogramming provide chances to generate a completely different cell type from an original cell source by artificially modulating the microenvironments or gene expressions pattern of cells. Although hepatocytes normally only reside in the liver, the hepatic program can be induced in skin-derived fibroblasts by expressing defined extrinsic transcription factors. These induced hepatocyte-like cells have hepatocyte-specific properties and functionally restore damaged hepatic tissues after transplantation. On the other hand, hepatocytes themselves can be converted into biliary lineage cells as a causative factor of hepatic diseases. Thus, blockade of such disease-related reprogramming of the hepatic fate will become a new therapeutic strategy for refractory diseases in the liver. Moreover, hepatocytes could partially accept the pancreatic program by expressing transcription factors required for pancreas development, suggesting that insulin-producing cells could be generated from hepatocytes and used to treat diabetes. The above-mentioned progress will stimulate studies on the molecular nature of cellular identity and plasticity in hepatocytes, and contribute to the development of potential therapies for liver diseases.
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U2 - 10.1016/j.gde.2013.04.006
DO - 10.1016/j.gde.2013.04.006
M3 - Review article
C2 - 23702217
AN - SCOPUS:84883801192
VL - 23
SP - 579
EP - 584
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
SN - 0959-437X
IS - 5
ER -