Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells
Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells
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DOI：
10.1016/j.bbrc.2005.08.136
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发表时间：
2005-10-21
影响因子：
3.1
通讯作者：
Terada, Y
中科院分区：
文献类型：
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作者：
Kobayashi, T;Tanaka, H;Terada, Y
胚胎干细胞具有分化为各种祖细胞的潜能。我们在体外和体内研究了小鼠胚胎干细胞向肾小管细胞分化的能力。将Wnt4 cDNA稳定转染到小鼠胚胎干细胞（Wnt4-ES细胞）后，采用悬滴培养法诱导未分化的胚胎干细胞向胚状体（EBs）分化。在培养过程中，水通道蛋白-2 (AQP2) mRNA和蛋白在15-20天内表达。在肝细胞生长因子（HGF）和激活素a的存在下，Wnt4-EBs中AQP2的表达增强。接下来，我们将Wnt4-EBs移植到小鼠肾皮质进行了体内实验。移植后4周，肾脏中部分表达AQP2的eb来源细胞组装成管状结构。总之，我们的体外和体内实验揭示了两个新的发现：第一，培养的Wnt4-EBs具有向肾小管细胞分化的能力；第二，Wnt4、HGF和激活素A可能促进胚胎干细胞向肾小管细胞的分化。(c) 2005爱思唯尔公司版权所有。
Embryonic stem (ES) cells have the potential to differentiate into various progenitor cells. Here we investigated the capacity of mouse ES cells to differentiate into renal tubular cells both in vitro and in vivo. After stably transfecting Wnt4 cDNA to mouse ES cells (Wnt4-ES cells), undifferentiated ES cells were incubated by the hanging drop culture method to induce differentiation to embryoid bodies (EBs). During culturing of the EBs derived from the Wnt4-ES cells, aquaporin-2 (AQP2) mRNA and protein were expressed within 15-20 days. The expression of AQP2 in Wnt4-EBs was enhanced in the presence of hepatocyte growth factor (HGF) and activin A. We next performed in vivo experiments by transplanting the Wnt4-EBs into the mouse renal cortex. Four weeks after transplantation, some portions of the EB-derived cells expressing AQP2 in the kidney assembled into tubular-like formations. In conclusion, our in vitro and in vivo experiments revealed two new findings: first, that cultured Wnt4-EBs have an ability to differentiate into renal tubular cells; and second, that Wnt4, HGF, and activin A may promote the differentiation of ES cells to renal tubular cells. (c) 2005 Elsevier Inc. All rights reserved.