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体外和体内来源的心脏祖细胞中长链非编码RNA(lncRNA)的表征与分析

Characterization and analysis of long non-coding rna (lncRNA) in In Vitro- and Ex Vivo-derived cardiac progenitor cells.

作者信息

Arnone Baron, Chen Jake Y, Qin Gangjian

机构信息

Department of Biomedical Engineering, School of Medicine & School of Engineering, UAB, Birmingham, AL, United States of America.

Informatics Institute, School of Medicine, UAB, Birmingham, AL, United States of America.

出版信息

PLoS One. 2017 Jun 22;12(6):e0180096. doi: 10.1371/journal.pone.0180096. eCollection 2017.

Abstract

Recent advancements in cell-based therapies for the treatment of cardiovascular disease (CVD) show continuing promise for the use of transplanted stem and cardiac progenitor cells (CPCs) to promote cardiac restitution. However, a detailed understanding of the molecular mechanisms that control the development of these cells remains incomplete and is critical for optimizing their use in such therapy. Long non-coding (lnc) RNA has recently emerged as a crucial class of regulatory molecules involved in directing a variety of critical biological processes including development, homeostasis and disease. As such, a rising body of evidence suggests that they also play key regulatory roles in CPC development, though many questions remain regarding the expression landscape and specific identity of lncRNA involved in this process. To address this, we performed whole transcriptome sequencing of two murine CPC populations-Nkx2-5 EmGFP reporter-sorted embryonic stem (ES) cell-derived and ex vivo, cardiosphere-derived-in an effort to characterize their lncRNA profiles and potentially identify novel CPC regulators. The resulting sequencing data revealed an enrichment in both CPC populations for a panel of previously-identified lncRNA genes associated with cardiac differentiation. Additionally, a total of 1,678 differentially expressed and as-of-yet unannotated, putative lncRNA genes were found to be enriched for in the two CPC populations relative to undifferentiated ES cells.

摘要

用于治疗心血管疾病(CVD)的基于细胞的疗法的最新进展显示,移植干细胞和心脏祖细胞(CPC)用于促进心脏恢复具有持续的前景。然而,对控制这些细胞发育的分子机制的详细了解仍然不完整,这对于优化它们在此类疗法中的应用至关重要。长链非编码(lnc)RNA最近已成为一类关键的调节分子,参与指导包括发育、体内平衡和疾病在内的各种关键生物学过程。因此,越来越多的证据表明它们在CPC发育中也起着关键的调节作用,尽管关于参与这一过程的lncRNA的表达谱和具体特性仍有许多问题。为了解决这个问题,我们对两个小鼠CPC群体进行了全转录组测序——Nkx2-5 EmGFP报告基因分选的胚胎干细胞(ES)来源的和体外心脏球衍生的——以努力表征它们的lncRNA谱并潜在地鉴定新的CPC调节因子。所得的测序数据显示,两个CPC群体中与心脏分化相关的一组先前鉴定的lncRNA基因均有富集。此外,相对于未分化的ES细胞,在两个CPC群体中总共发现1678个差异表达且尚未注释的假定lncRNA基因有富集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a6d/5481004/0234f251d7ab/pone.0180096.g001.jpg

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