Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle.
Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle.
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DOI：
10.1186/s12864-018-4646-5
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发表时间：
2018-04-10
期刊：
影响因子：
4.4
通讯作者：
Donadeu FX
中科院分区：
文献类型：
--
作者：
Ioannidis J;Donadeu FX
循环miRNA作为健康和疾病中组织功能生物标志物的潜力已在人类中得到广泛证实。此外，循环miRNA生物标志物为提高家畜物种的生产力提供了显著的潜力，然而，这种潜力受到缺乏关于这些物种中循环miRNA群体的性质和来源的信息的阻碍。此外，最初提出作为人类特定组织或疾病的稳健生物标志物的许多miRNA后来被证明不是组织特异性的，因此实际上具有有限的生物标志物效用。在这项研究中，我们全面分析了牛的血浆和血液细胞组分中的miRNA谱，目的是鉴定组织来源的miRNA，这些miRNA可能用作这一重要食用动物物种组织功能的生物标志物。使用小RNA测序，我们鉴定了92种在血浆中的表达显著高于配对血细胞样品（n = 4头奶牛）。使用RT-qPCR（n = 10头奶牛）对10种miRNA中的8种验证血浆和细胞组分之间的miRNA水平差异。在血浆中发现富集的miRNA中，我们证实了miR-122（肝脏），miR-133 a（肌肉）和miR-215（肠）是组织富集的，如其他物种所报道的那样。在不同组织中对其他miRNA的分析鉴定出人类同源物miR-802在肝脏中高度富集。这些结果提供了牛循环miRNAs来源的新信息，并可显著促进家畜生产相关组织生物标志物的鉴定。特别是，miR-802，一种以前在牛中未发现的循环miRNA，据报道可以调节胰岛素敏感性和脂质代谢，因此可能提供肝功能的特异性生物标志物，这是奶牛产后负能量平衡的关键参数。本文的在线版本（10.1186/s12864-018-4646-5）包含补充材料，可供授权用户使用。
The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. In addition, circulating miRNA biomarkers offer significant potential towards improving the productivity of livestock species, however, such potential has been hampered by the absence of information on the nature and source of circulating miRNA populations in these species. In addition, many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and thus to actually have limited biomarker utility. In this study, we comprehensively analysed miRNA profiles in plasma and cell fractions of blood from cattle with the aim to identify tissue-derived miRNAs which may be useful as biomarkers of tissue function in this important food animal species. Using small RNA sequencing, we identified 92 miRNAs with significantly higher expression in plasma compared to paired blood cell samples (n = 4 cows). Differences in miRNA levels between plasma and cell fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows). Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR-133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for other species. Profiling of additional miRNAs across different tissues identified the human homologue, miR-802, as highly enriched specifically in liver. These results provide novel information on the source of bovine circulating miRNAs and could significantly facilitate the identification of production-relevant tissue biomarkers in livestock. In particular, miR-802, a circulating miRNA not previously identified in cattle, can reportedly regulate insulin sensitivity and lipid metabolism, and thus could potentially provide a specific biomarker of liver function, a key parameter in the context of post-partum negative energy balance in dairy cows. The online version of this article (10.1186/s12864-018-4646-5) contains supplementary material, which is available to authorized users.
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