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Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.
Developmental Cell ( IF 10.7 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.devcel.2020.07.006
Kitchener D Wilson 1 , Mohamed Ameen 2 , Hongchao Guo 3 , Oscar J Abilez 3 , Lei Tian 3 , Maxwell R Mumbach 4 , Sebastian Diecke 5 , Xulei Qin 3 , Yonggang Liu 3 , Huaxiao Yang 3 , Ning Ma 3 , Sadhana Gaddam 4 , Nathan J Cunningham 3 , Mingxia Gu 3 , Evgenios Neofytou 3 , Maricela Prado 3 , Thomas B Hildebrandt 6 , Ioannis Karakikes 7 , Howard Y Chang 4 , Joseph C Wu 8
Affiliation  

Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we use primate pluripotent stem-cell-derived cardiomyocytes that mimic fetal cardiomyocytes in vitro to discover hundreds of ERV transcripts from the primate-specific MER41 family, some of which are regulated by the cardiogenic transcription factor TBX5. The most significant of these are located within BANCR, a long non-coding RNA (lncRNA) exclusively expressed in primate fetal cardiomyocytes. Functional studies reveal that BANCR promotes cardiomyocyte migration in vitro and ventricular enlargement in vivo. We conclude that recently evolved TE loci such as BANCR may represent potent de novo developmental regulatory elements that can be interrogated with species-matching pluripotent stem cell models.



中文翻译:


内源性逆转录病毒衍生的 lncRNA BANCR 促进人类和非人类灵长类动物的心肌细胞迁移。



转座元件(TE)包含近一半的人类基因组,通常被转录或表现出顺式调节特性,在心脏发育等特定过程中具有未知的功能。就内源性逆转录病毒 (ERV)(TE 亚类)而言,实验研究受到限制,因为许多病毒是灵长类动物特异性或人类特异性的。在这里,我们使用灵长类多能干细胞衍生的心肌细胞在体外模拟胎儿心肌细胞,发现了灵长类特异性 MER41 家族的数百种 ERV 转录本,其中一些转录因子受心原性转录因子 TBX5 调节。其中最重要的位于BANCR内,这是一种专门在灵长类动物胎儿心肌细胞中表达的长非编码 RNA (lncRNA)。功能研究表明, BANCR在体外可促进心肌细胞迁移,在体内可促进心室扩大。我们的结论是,最近进化的 TE 基因座(例如BANCR)可能代表有效的从头发育调控元件,可以用物种匹配的多能干细胞模型进行研究。

更新日期:2020-09-28
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