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Mbd3促进原代人成纤维细胞的重编程。

Mbd3 Promotes Reprogramming of Primary Human Fibroblasts.

作者信息

Jaffer Sajjida, Goh Pollyanna, Abbasian Mahnaz, Nathwani Amit C

机构信息

Department of Haematology, University College London, Cancer Institute, London, UK.

Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free NHS Trust, London, UK.

出版信息

Int J Stem Cells. 2018 Nov 30;11(2):235-241. doi: 10.15283/ijsc18036.

Abstract

Mbd3 (Methyl-CpG binding domain protein), a core member of NuRD (nucleosome remodelling and deacetylation) is essential for embryogenesis. However, its role in reprogramming of somatic cells into induced pluripotent stem cells (iPSC) remains controversial. Some reports suggest that Mbd3 inhibits pluripotency, whilst others show that it greatly enhances reprogramming efficiency. Our study is the first to assess the role of on reprogramming of primary human fibroblasts using Yamanaka episomal plasmids (Reprogramming factors (RF) under feeder-free conditions. We showed that shRNA-mediated partial depletion of resulted in >5-fold reduction in the efficiency of reprogramming of primary human fibroblasts. Furthermore, iPSC that emerged after knock-down of were incapable of trilineage differentiation even though they expressed all markers of pluripotency. In contrast, over-expression of the isoform along with the Yamanaka episomal plasmids increased the number of fibroblast derived iPSC colonies by at least two-fold. The resulting colonies were capable of trilineage differentiation. Our results, therefore, suggest that appears to play an important role in reprogramming of primary human fibroblasts, which provides further insight into the biology of reprogramming but also has direct implication for translation of iPSC to clinic.

摘要

Mbd3(甲基化CpG结合域蛋白)是核小体重塑与去乙酰化复合物(NuRD)的核心成员,对胚胎发育至关重要。然而,其在体细胞重编程为诱导多能干细胞(iPSC)过程中的作用仍存在争议。一些报告表明Mbd3抑制多能性,而另一些报告则显示它能大大提高重编程效率。我们的研究首次使用山中伸弥附加体质粒在无饲养层条件下评估Mbd3对原代人成纤维细胞重编程的作用(重编程因子(RF))。我们发现,shRNA介导的Mbd3部分缺失导致原代人成纤维细胞重编程效率降低超过5倍。此外,敲低Mbd3后出现的iPSC即使表达了所有多能性标志物,也无法进行三系分化。相反,与山中伸弥附加体质粒一起过表达Mbd3异构体可使成纤维细胞来源的iPSC集落数量增加至少两倍。产生的集落能够进行三系分化。因此,我们的结果表明Mbd3似乎在原代人成纤维细胞重编程中起重要作用,这不仅为深入了解重编程生物学提供了进一步的见解,也对iPSC向临床应用的转化具有直接意义。

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