Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation.
Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation.
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人类多能向心肌细胞分化过程中的全局 RNA 编辑鉴定和表征
DOI：
10.1016/j.omtn.2021.10.001
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Chen J;Liu HF;Qiao LB;Wang FB;Wang L;Lin Y;Liu J
RNA编辑广泛参与干细胞分化和发育;然而，人类心肌细胞分化过程中的RNA编辑事件尚未被表征和阐明。在这里，我们确定了全基因组RNA编辑位点，并系统地表征了它们在人类心肌细胞分化的四个阶段中的基因组分布。结果发现，ADAR 1的表达水平影响腺苷到肌苷（A-to-I）编辑位点的总体数量，但不影响编辑程度。接下来，我们分别鉴定了43、163、544和141个RNA编辑位点，这些位点分别导致氨基酸序列的变化、选择性剪接的变异、miRNA与靶标结合的改变以及基因表达的变化。总体而言，RNA编辑表现出阶段特异性模式，具有211个阶段共享的编辑位点。有趣的是，心脏特异性编辑基因丰富了心肌收缩和心脏疾病相关通路，从RNA编辑的角度强调了心肌细胞分化与心脏疾病之间的联系。最后，发现这些RNA编辑位点也与几种先天性和非先天性心脏病有关。总之，我们的研究为心肌细胞分化提供了一个新的视角，并提供了更多的机会来了解细胞命运决定的机制，这可以促进心脏再生医学和人类心脏病治疗的发展。本研究全面鉴定和表征了人类多能细胞向心肌细胞分化的4个阶段中的RNA编辑事件，为心脏再生医学的发展提供了新的思路。
RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases. This study provides a comprehensive identification and characterization of RNA editing events during four human pluripotent-to-cardiomyocyte differentiation stages, which can promote the development of cardiac regenerative medicine and offer new ideas for the therapies of human heart diseases.
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影响因子：
14.9
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Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
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