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Title :Differentiation of mouse and human ES cells into hepatic lineages
Authors :Shiraki, Nobuaki
Umeda, Kahoko
Sakashita, Naomi
Takeya, Motohiro
Kume, Kazuhiko
Kume, Shoen
Issue Date :Jul-2008
Citation jtitle :Genes to cells
vol. :13
no. :7
start page :731
end page :746
Abstract :We recently reported a novel method to induce embryonic stem (ES) cells differentiate into an endodermal fate, especially pancreatic, using a supporting cell line. Here we describe the modified culture condition with the addition and withdrawal of secreted growth factors could induce ES cells to selectively differentiate into a hepatic fate efficiently. The signaling of BMP and FGF that have been implicated in hepatic differentiation during normal embryonic development are shown to play pivotal roles in generating hepatic cells from the definitive endoderm derived from ES cells. Moreover, the expression of AFP, Albumin or a biliary molecular marker appeared sequentially thus suggested the differentiation of ES cells recapitulated normal developmental processes of liver. The ES cell-derived differentiated cells showed evidence of glycogen storage, secreted Albumin, exhibited drug metabolism activities and expressed a set of cytochrome or drug conjugate enzymes, drug transporters specifically expressed in mature hepatocytes. With the same procedure, human ES cells also gave rise to cells with mature hepatocytes’ characteristics. In conclusion, this novel procedure for hepatic differentiation will be useful for elucidation of molecular mechanisms of hepatic fate decision at gut regionalization, and could represent an attractive approach for a surrogate cell source for pharmaceutical studies such as toxicology.
Type Local :雑誌掲載論文
Publisher :Blackwell Publishing
Rights :© 2008 by the Molecular Biology Society of Japan/Blackwell Publishing
URI :http://hdl.handle.net/2298/11006
Appears in Collections:Journal Article (Institute of Molecular Embryology and Genetics )
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/11006