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人母乳细胞外囊泡中长链非编码RNA的检测:对儿童早期发育的影响

Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development.

作者信息

Karlsson Oskar, Rodosthenous Rodosthenis S, Jara Calvin, Brennan Kasey J, Wright Robert O, Baccarelli Andrea A, Wright Rosalind J

机构信息

a Center for Molecular Medicine , Department of Clinical Neuroscience , Karolinska Institute , Stockholm , Sweden.

b Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.

出版信息

Epigenetics. 2016 Oct 2;11(10):721-729. doi: 10.1080/15592294.2016.1216285. Epub 2016 Nov 1.

Abstract

Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR, GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho > 0.9; P < 0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.

摘要

母乳对人类婴儿的发育具有许多已被证实的有益影响,但影响这些发育途径的母乳成分尚未完全阐明。越来越多的证据表明,包裹在细胞外囊泡(EVs)中的非编码RNA代表了母婴之间交流的重要机制。鉴于长链非编码RNA(lncRNAs)在基因表达和发育中的关键作用,它们尤其受到关注。然而,尚不清楚母乳来源的细胞外囊泡中是否含有lncRNAs。我们使用qRT-PCR来确定从人母乳中分离的细胞外囊泡是否含有先前报道的对发育过程重要的lncRNAs。在分析的30份母乳样本的细胞外囊泡中,我们检测到了87种筛选的lncRNAs中的55种,并且在超过90%的样本中检测到了CRNDE、DANCR、GAS5、SRA1和ZFAS1。GAS5、SNHG8和ZFAS1的水平高度相关(斯皮尔曼相关系数>0.9;P<0.0001),这可能表明这些lncRNAs加载到母乳细胞外囊泡中是由相同的途径调控的。检测到的lncRNAs是参与免疫细胞调节和代谢等过程的重要表观遗传调节因子。它们可能作用于后代的一系列受体细胞,并且可能对儿童的发育和健康至关重要。有必要进行进一步的实验和流行病学研究,以确定母乳细胞外囊泡包裹的lnRNAs在母婴信号传递中的影响。

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