SmedOB1 is Required for Planarian Homeostasis and Regeneration.

SmedOB1 is Required for Planarian Homeostasis and Regeneration.
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SmedOB1 是涡虫稳态和再生所必需的

DOI:
10.1038/srep34013
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发表时间:
2016-09-22
期刊:
影响因子:
4.6
通讯作者:
Songyang Z
Songyang Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yin S;Huang Y;Zhangfang Y;Zhong X;Li P;Huang J;Liu D;Songyang Z

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扁形虫是一种新兴的模型,由于其独特的成体干细胞(ASCs),可用于研究体内平衡和再生。此前,研究发现真涡虫与哺乳动物有相同的TTAGGG染色体末端和端粒聚合酶,但它们的端粒保护蛋白尚未被鉴定。在Schmidtea medialacea中,我们鉴定了具有OB-折叠(SmedOB 1)的人类端粒保护1(POT 1)的同源物。SmedOB 1在物种间进化保守,并且在整个身体中普遍表达。用SmedOB 1双链RNA(dsRNA)喂养导致头部和咽部的稳态异常。此外,几个ASC后代标记下调,再生受损。我们发现SmedOB 1是端粒DNA-蛋白质复合物形成所必需的,并且在体外与端粒TTAGGG序列相关。此外,SmedOB 1 RNAi对真涡虫DNA损伤和凋亡信号的影响也显著。我们也证实了这些表型在三角洲,另一种扁形虫。我们的工作确定了一个新的端粒相关蛋白SmedOB 1在真涡虫,这是必需的真涡虫的稳态和再生。SmedOB 1的系统发育和功能保守性提供了一种机制,通过该机制,涡虫维持端粒和基因组的稳定性,以确保其永生,并为人类的再生医学提供了启示。
The planarian flatworm is an emerging model that is useful for studying homeostasis and regeneration due to its unique adult stem cells (ASCs). Previously, planaria were found to share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins have not yet been identified. InSchmidtea mediterranea, we identified a homologue of the human protection of telomeres 1 (POT1) with an OB-fold (SmedOB1). SmedOB1 is evolutionarily conserved among species and is ubiquitously expressed throughout the whole body. Feeding with SmedOB1 double-stranded RNAs (dsRNAs) led to homeostasis abnormalities in the head and pharynx. Furthermore, several ASC progeny markers were downregulated and regeneration was impaired. Here we found that SmedOB1 is required for telomeric DNA-protein complex formation and it associates with the telomere TTAGGG sequencein vitro. Moreover, DNA damage and apoptosis signals in planarian were significantly affected by SmedOB1 RNAi. We also confirmed these phenotypes inDugesia japonica,another flatworm species. Our work identified a novel telomere-associated protein SmedOB1 in planarian, which is required for planarian homeostasis and regeneration. The phylogenetic and functional conservations of SmedOB1 provide one mechanism by which planarians maintain telomere and genome stability to ensure their immortality and shed light on the regeneration medicine of humans.
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