アクティブボード・２０１５年　６月
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研究発表を行った学会；
・第３７回日本分子生物学会年会
　２０１４年１１月２５日〜２７日（横浜）
タイトル；Redefining the in vivo Origin of Nephron Progenitors Enables Generation of Three-dimensional Kidney Structures from Pluripotent Stem Cells in vitro.
発表者；太口　敦博　氏
　　　（熊本大学　発生医学研究所　腎臓発生分野）
Abstract；
Generation of the kidney in vitro has been a challenge because reconstitution of the three-dimensional nephron structures including glomeruli and nephric tubules is a prerequisite for the kidney functions. Adult kidney derives from caudally located embryonic metanephros which is composed of metanephric mesenchyme (MM) and the ureteric bud (UB), both of which are reportedly derived from common intermediate mesoderm (IM). Most nephron components are derived from metanephric nephron progenitors in the MM. However, how the IM differentiates from nascent mesoderm and how the MM develops caudally along the IM are largely unknown.
Here we revealed that the origin of MM is caudal T+ precursors at embryonic day 8.5, and that developmentally distinct from Osr1+ anteriorly located IM, which primarily contribute to the UB. We further identified the key molecules for the MM induction from such embryonic T+ cells in vitro, including posteriorization with a high concentration of Wnt agonist, followed by its graded attenuation and stage-specific growth factors. Finally, by applying this protocol to the mouse and human pluripotent stem cells, metanephric nephron progenitors were obtained. Importantly, when cocultured with Wnt4 expressing feeder cells or embryonic spinal cords, they formed the three-dimensional kidney structures, including renal tubules and glomeruli with podocytes, which have never been obtained in the previous reports.
Thus, by re-evaluating the developmental origins of metanephric progenitors, we have provided key insights into kidney specification in vivo and taken important steps toward kidney organogenesis in vitro.