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CD44基因缺陷型小鼠来源的诱导多能干细胞的产生:CD44基因缺陷型诱导多能干细胞

Generation of CD44 gene-deficient mouse derived induced pluripotent stem cells: CD44 gene-deficient iPSCs.

作者信息

Song Zhenwei, Ji Qianqian, Zhao Haijing, Nie Yu, He Zuyong, Chen Yaosheng, Cong Peiqing

机构信息

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Higher Education Mega Center, Guangzhou, 510006, People's Republic of China,

出版信息

In Vitro Cell Dev Biol Anim. 2014 Oct;50(9):874-82. doi: 10.1007/s11626-014-9786-6. Epub 2014 Jun 21.

Abstract

Induced pluripotent stem cells (iPSCs) show good promise for the treatment of defects caused by numerous genetic diseases. Herein, we successfully generated CD44 gene-deficient iPSCs using Oct4, Sox2, Klf4, and vitamin C. The generated iPSCs displayed a characteristic morphology similar to the well-characterized embryonic stem cells. Alkaline phosphatase, cell surface (SSEA1, NANOG, and OCT4), and pluripotency markers were expressed at high levels in these cells. The iPSCs formed teratomas in vivo and supported full-term development of constructed porcine embryos by inter-species nuclear transplantation. Importantly, incubation with trichostatin A increased the efficiency of iPSCs generation by increasing the histone acetylation levels. Moreover, more iPSCs colonies appeared following cell passaging during colony picking, thus increasing the effectiveness of iPSCs selection. Thus, our work provides essential stem cell materials for the treatment of genetic diseases and proposes a novel strategy to enhance the efficiency of induced reprogramming.

摘要

诱导多能干细胞(iPSC)在治疗由多种遗传疾病引起的缺陷方面显示出良好的前景。在此,我们使用Oct4、Sox2、Klf4和维生素C成功生成了CD44基因缺陷的iPSC。所生成的iPSC表现出与特征明确的胚胎干细胞相似的特征形态。碱性磷酸酶、细胞表面标志物(SSEA1、NANOG和OCT4)以及多能性标志物在这些细胞中高水平表达。iPSC在体内形成畸胎瘤,并通过种间核移植支持构建的猪胚胎的足月发育。重要的是,用曲古抑菌素A孵育通过提高组蛋白乙酰化水平提高了iPSC的生成效率。此外,在集落挑选过程中细胞传代后出现了更多的iPSC集落,从而提高了iPSC选择的有效性。因此,我们的工作为遗传疾病的治疗提供了重要的干细胞材料,并提出了一种提高诱导重编程效率的新策略。

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