アクティブボード・２０１２年　７月
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研究発表を行った学会；
・Joint Meeting of JSDB 45th & JSCB 64th
　２０１２年　５月２８日〜３１日（神戸）

タイトル；A specific amino acid metabolic state of human ES/iPS cells and its significance.

発表者；白木　伸明　氏
　　　（熊本大学　発生医学研究所　多能性幹細胞分野）
Abstract；
Embryonic stem (ES) cells possess a characteristic high rate of proliferation and a short G1 phase; they have an unlimited ability to replicate as well as the potential to differentiate into most cell types in an organism, including hepatic lineage. Recent studies showed that mouse ES cells are in a high-flux metabolic state, showing a high dependence on threonine catabolism, in particular. Marked differences in the differentiation propensity exist among human ES (hES) cell lines and form an obstacle for the directed differentiation of hES/iPS cells in vitro.
Here, we identified a specific dependence of the pluripotent human ES/iPS cells on a particular amino acid for their growth. We have established a differentiation procedure for human ES/iPS cells to differentiate into the definitive endoderm derivatives of the pancreas and liver. To establish a more endoderm selective differentiation method, we focused on the differences of amino acid metabolisms between the undifferentiated and differentiated definitive endoderm cells. When cultured in media deprived of the particular amino acid, undifferentiated human ES/iPS cells rapidly ceased to proliferate and apoptosis occurred, which resulted in an increased proportion of Sox17-positive definitive endoderm cells. Further differentiation into hepatic lineages was potentiated, to yield a 3-fold increase in Albumin secretion.
In this study, a novel human ES/iPS cell differentiation system, based on the difference of a specific amino acid metabolism between undifferentiated cells and differentiated cells, is established. By using the media deprived of a particular amino acid, undifferentiated cells can be specifically eliminated during endoderm differentiation. This method is useful for directing human ES/iPS cell lines that are resistant to differentiation to achieve a higher differentiation efficiency.