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Stem Cells:同济大学康九红教授课题组揭示lncRNA-1604通过miR-200c/ZEB调控干细胞定向神经分化的重要

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摘要 : 2017年12月5日,国际干细胞领域著名刊物《Stem Cells》在线发表了同济大学生命科学与技术学院康九红教授课题组题为 “Long noncoding RNA-1604 orchestrates neural differentiation through the miR-200c/ZEB axis”的研究成果。

2017年12月5日,国际干细胞领域著名刊物《Stem Cells》在线发表了同济大学生命科学与技术学院康九红教授课题组题为 “Long noncoding RNA-1604 orchestrates neural differentiation through the miR-200c/ZEB axis”的研究成果。文章着重揭示了长链非编码RNA-1604(lncRNA-1604)作为miR-200c/ZEB的竞争性内源RNA(ceRNA)而调控干细胞定向神经细胞分化的重要功能与新机制。瓮荣硕士和陆晨琪博士为本文的共同第一作者,康九红教授和汪贵英副教授为本文的共同通讯作者。

哺乳动物从早期全能性细胞逐步发育成个体的过程是复杂而且精细的,主要依赖于转录因子、表观修饰、信号分子的共同参与和精确控制。干细胞作为一类能够在体外培养且具有完整发育全能性的细胞,是解析多能性维持、细胞命运决定和个体发育机制的重要工具。阐明干细胞定向神经细胞分化的调控机制不仅有利于理解神经发育过程,同时还有望为神经退行性疾病的干细胞治疗提供高质量的神经前体细胞。

本项研究发现了一条小鼠干细胞和神经分化过程中持续高表达的长链非编码rna(lncRNA-1604),敲降lncRNA-1604的表达水平可以显著抑制干细胞向神经细胞分化。生物信息学预测和机制分析显示lncRNA-1604可以作为miR-200c的ceRNA进而调控ZEB1/2在小鼠干细胞定向神经细胞分化中的功能。这项研究不仅揭示了lncRNA-1604、miR-200c和ZEB1/2在干细胞定向神经细胞分化的重要功能,同时阐明了lncRNA-1604/miR-200c/ZEB定向调控干细胞神经细胞分化的新机制。

原文链接:

Long noncoding RNA-1604 orchestrates neural differentiation through the miR-200c/ZEB axis

原文摘要:

Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural differentiation is helpful not only for understanding neural development, but also for obtaining high-quality neural progenitor cells required by stem cell therapy of neurodegenerative diseases. Here, we found that long noncoding RNA 1604 (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation, and knockdown of lncRNA-1604 significantly repressed neural differentiation of mouse ESCs both in vitro and in vivo. BioInformatics prediction and mechanistic analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during neural differentiation. Furthermore, we also demonstrated the critical role of miR-200c and ZEB1/2 in mouse neural differentiation. Either introduction of miR-200c sponge or overexpression of ZEB1/2 significantly reversed the lncRNA-1604 knockdown-induced repression of mouse ESC neural differentiation. Collectively, these findings not only identified a previously unknown role of lncRNA-1604 and ZEB1/2, but also elucidated a new regulatory lncRNA-1604/miR-200c/ZEB axis in neural differentiation.

DOI:10.1002/stem.2749

作者:康九红 点击:

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