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binxman木蟲 (著名寫手)
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[求助]
100金幣求助英譯中,禁止機(jī)器翻譯,關(guān)于干細(xì)胞的,謝謝!
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Tbx3 improves the germ-line competency of induced pluripotent stem cells. Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells. The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies. |
金蟲 (小有名氣)
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Tbx3促進(jìn)誘導(dǎo)多能干細(xì)胞的生殖細(xì)胞系能力 誘導(dǎo)多能干細(xì)胞(iPS)可通過將確定的因子引入體細(xì)胞的方法獲得。從小鼠胚胎成纖維細(xì)胞產(chǎn)生iPS細(xì)胞至少需要Oct4 (亦稱之為Pou5f1)、Sox2 和 Klf4 (我們稱之為OSK)的結(jié)合。有人根據(jù)綜合基因表達(dá)分析,認(rèn)為這些細(xì)胞組裝了胚胎干細(xì)胞(ESCs);但是,幾乎沒有研究測(cè)試iPS細(xì)胞在生殖組織的嵌合現(xiàn)象和定植尤其是生殖細(xì)胞系傳遞以及通過四倍體互補(bǔ)產(chǎn)生的iPS細(xì)胞生成活體生殖細(xì)胞系中的能力和效果。我們對(duì)在多能化和融合介導(dǎo)體細(xì)胞重新編程中起作用的ESC基因進(jìn)行基因組分析,顯示轉(zhuǎn)錄因子Tbx3顯著提高了iPS細(xì)胞的性能。iPS細(xì)胞生成OSK 和Tbx3 (OSKT),在促進(jìn)性腺產(chǎn)生生殖細(xì)胞及生殖細(xì)胞系傳遞頻率中都占有優(yōu)勢(shì)。但是,綜合基因表達(dá)不能區(qū)分OSK 和OSKT iPS 細(xì)胞。對(duì)ESC的Tbx3結(jié)合位點(diǎn)進(jìn)行基因組范圍的染色質(zhì)免疫沉淀測(cè)序分析提示,除了共享許多共同的下游調(diào)節(jié)靶基因包括Oct4, Sox2, Nanog 和 Smad1,Tbx3調(diào)節(jié)多能相關(guān)因子和重新編程因子。本研究強(qiáng)調(diào)了通過不同方法生成的iPS 細(xì)胞之間的內(nèi)在性質(zhì)的差異,強(qiáng)調(diào)了有必要在體外試驗(yàn)范圍之外精確地描述iPS細(xì)胞的特性。 |
木蟲 (著名寫手)
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