PIWI-interacting RNA (piRNA) signatures in human cardiac progenitor cells
PIWI-interacting RNA (piRNA) signatures in human cardiac progenitor cells
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DOI：
10.1016/j.biocel.2016.04.012
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发表时间：
2016-07-01
影响因子：
4
通讯作者：
Conaldi, Pier Giulio
中科院分区：
文献类型：
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作者：
Vella, Serena;Gallo, Alessia;Conaldi, Pier Giulio
心脏祖细胞，如心脏球和心脏球衍生的细胞，代表了心脏再生的有吸引力的细胞来源。PIWI相互作用RNA（piRNA）是一类有趣的小的非编码RNA，涉及表观遗传状态的调节、基因组完整性的维持和干细胞功能。虽然非编码RNA是心血管研究中的一个开拓性领域，但心脏祖细胞的皮尔纳特征尚未得到评估。我们通过微阵列分析了在心脏球、心脏球衍生细胞和心脏成纤维细胞中表达的15，311个piRNA。结果显示了一组差异表达的piRNA（倍数变化>= 2，p < 0.01）：与心球来源的细胞相比，在心球中641个piRNA上调，1，301个下调，而如果与心脏成纤维细胞相比，则分别有255个和708个piRNA上调和下调。与心脏成纤维细胞相比，我们还鉴定了181个在心脏球源性细胞中过表达的piRNA和129个下调的piRNA。生物信息学分析显示，下调的piRNA主要分布在少数染色体上，表明piRNA是以离散的基因组簇组织的。此外，生物信息学搜索显示，大多数上调的piRNA靶向转座子，特别是LINE-1类，通过qRT-PCR验证。这种减少也与AKT信号传导的激活有关，这对心脏再生是有益的。本研究首次显示了人类心脏祖细胞高度一致的皮尔纳表达模式，这可能是其不同再生能力的原因。此外，这种piRNome分析可能为表征心脏祖细胞提供新的方法，并可能为理解心脏再生的复杂分子机制提供新的思路。(C)2016作者爱思唯尔有限公司出版
Cardiac progenitors, such as cardiospheres and cardiosphere-derived cells, represent an attractive cell source for cardiac regeneration. The PIWI-interacting RNAs, piRNAs, are an intriguing class of small non coding RNAs, implicated in the regulation of epigenetic state, maintenance of genomic integrity and stem cell functions. Although non-coding RNAs are an exploiting field in cardiovascular research, the piRNA signatures of cardiac progenitors has not been evaluated yet.We profiled, through microarrays, 15,311 piRNAs expressed in cardiospheres, cardiosphere-derived cells and cardiac fibroblasts. Results showed a set of differentially expressed piRNAs (fold change >= 2, p < 0.01): 641 piRNAs were upregulated and 1,301 downregulated in the cardiospheres compared to cardiosphere-derived cells, while 255 and 708 piRNAs resulted up- and down-regulated, respectively, if compared to cardiac fibroblasts. We also identified 181 piRNAs that are overexpressed and 129 are downregulated in cardiosphere-derived cells respect to cardiac fibroblasts.Bioinformatics analysis showed that the deregulated piRNAs were mainly distributed on few chromosomes, suggesting that piRNAs are organized in discrete genomic clusters.Furthermore, the bioinformatics search showed that the most upregulated piRNAs target transposons, especially belonged to LINE-1 class, as validated by qRT-PCR. This reduction is also associated to an activation of AKT signaling, which is beneficial for cardiac regeneration.The present study is the first to show a highly consistent piRNA expression pattern for human cardiac progenitors, likely responsible of their different regenerative power. Moreover, this piRNome analysis may provide new methods for characterize cardiac progenitors and may shed new light on the understanding the complex molecular mechanisms of cardiac regeneration. (C) 2016 The Authors. Published by Elsevier Ltd.