Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro
Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro
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DOI：
10.1016/j.bbrc.2009.10.148
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发表时间：
2009-12-25
影响因子：
3.1
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Morizane, Ryuji;Monkawa, Toshiaki;Itoh, Hiroshi
胚胎干细胞具有无限的增殖能力和广泛的分化潜能，是肾脏再生治疗的一个有吸引力的来源。最近在诱导多能干细胞（iPS）产生方面的突破为人工生成的肾脏提供了另一个潜在来源。本研究的目的是了解如何将小鼠ES细胞和iPS细胞分化为肾系细胞。我们使用来自小鼠成纤维细胞的iPS细胞，通过转染四种转录因子，即Oct 4、Sox 2、c-Myc和Klf 4。Real-time PCR结果显示，诱导分化后的ES细胞和iPS细胞均表达肾系标志物。它还表明，肾小管特异性标志物KSP逐渐增加至第18天，尽管iPS细胞的分化比ES细胞慢。结果表明，肾谱系细胞可以从小鼠ES和iPS细胞分化。检测了几种诱导因子对细胞分化的影响。在ES细胞中，GDNF和BMP 7均促进ES细胞向后肾间充质细胞分化，Activin促进ES细胞向肾小管细胞分化。激活素也促进iPS细胞向肾小管细胞的分化，尽管这种促进作用低于ES细胞。ES和iPS细胞具有向肾系细胞分化的潜能，它们将成为肾再生治疗的有吸引力的资源。这种分化在ES和iPS细胞中均被激活素增强。(C)2009 Elsevier Inc. All rights reserved.
Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells. (C) 2009 Elsevier Inc. All rights reserved.