Background

Down syndrome (DS), caused by trisomy 21, is the most common human chromosomal disorder. Hippocampal abnormalities have been believed to be responsible for the DS developmental cognitive deficits. Cumulative evidences indicated that non-coding RNAs (ncRNAs) participated in brain development and function. Currently, few was known whether dysregulated ncRNAs existed in DS whether the dysregulated ncRNAs played important pathology roles in DS.

Objective

The purpose of this study was generating an overview map of the dysregulated ncRNAs in DS, including the microRNA (miRNA), long ncRNA (lncRNA) and circular RNA (circRNAs). DS mouse models are invaluable tools for further mechanism and therapy studies.

Methods

The well-studied DS mouse model Dp(16)1/Yey was used in this study as it contains the trisomy of the whole human chromosome 21 syntenic region on mouse chromosomes 16. Hippocampi were isolated from pups of seven-days-old. Libraries for miRNA, lncRNA and circRNAs were constructed separately, and the next generation sequencing method was utilized.

Results

Differentially expressed (DE) miRNAs, lncRNAs and circRNAs were reported. Relative few regulating relationship were found between the DE miRNAs and DE mRNAs. LncRNAs originated from the trisomic regions expressed in clusters, but not all of them were 1.5-fold increased expressed. Dramatic DE circular RNAs were found in the DS hippocampus. The host genes of the DE circRNAs were enriched on functions which were well-known impaired in DS, e.g. long-term-potentiation, glutamatergic synapse, and GABAergic synapse.

Conclusions

We generated the first DS developmental hippocampal ncRNA transcriptome map. This work laid foundations for further investigations on role of ncRNAs in hippocampal functions.

中文翻译：

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使用小鼠模型对唐氏综合症海马非编码 RNA 转录组进行比较分析。

背景

由 21 三体引起的唐氏综合症 (DS) 是最常见的人类染色体疾病。海马异常被认为是造成 DS 发育认知缺陷的原因。累积证据表明，非编码 RNA (ncRNA) 参与了大脑的发育和功能。目前，对于 DS 中是否存在失调的 ncRNAs 是否在 DS 中发挥重要的病理作用知之甚少。

客观的

本研究的目的是生成 DS 中失调的 ncRNA 的概览图，包括 microRNA (miRNA)、长 ncRNA (lncRNA) 和环状 RNA (circRNA)。DS 小鼠模型是进一步机制和治疗研究的宝贵工具。

方法

本研究中使用了经过充分研究的 DS 小鼠模型Dp(16)1/Yey，因为它包含小鼠 16 号染色体上整个人类 21 号染色体同线区的三体性。海马是从 7 天大的幼崽中分离出来的。分别构建miRNA、lncRNA和circRNA的文库，并利用下一代测序方法。

结果

报告了差异表达 (DE) miRNA、lncRNA 和 circRNA。在DE miRNAs和DE mRNAs之间发现相对较少的调节关系。LncRNAs 起源于成簇表达的三体区域，但并非所有的表达量都增加了 1.5 倍。在 DS 海马体中发现了显着的 DE 环状 RNA。DE circRNA 的宿主基因富集了众所周知的 DS 受损功能，例如长时程增强、谷氨酸能突触和 GABA 能突触。

结论

我们生成了第一个 DS 发育海马 ncRNA 转录组图谱。这项工作为进一步研究 ncRNA 在海马功能中的作用奠定了基础。