Comparative analysis of the down syndrome hippocampal non-coding RNA transcriptomes using a mouse model
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Genes & Genomics https://doi.org/10.1007/s13258-020-00996-8
RESEARCH ARTICLE
Comparative analysis of the down syndrome hippocampal non-coding RNA transcriptomes using a mouse model Zhaowei Cai1 · Zhilan Xiao2 · Yufang Wang2 · Huazhen Liu2 · Kangdi Zhang2 · Xiaoning Zhen2 · Xiaoling Jiang2 Received: 5 August 2020 / Accepted: 7 September 2020 © The Genetics Society of Korea 2020
Abstract 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-termpotentiation, 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. Keywords Down syndrome · Transcriptome · Hippocampus · microRNA · lncRNA · Circular RNA
Introduction Down syndrome (DS), caused by chromosome 21 (HSA21) trisomy, is the most frequently occurred human chromosomal disorder (Antonarakis 2017). Deficits in learning and memory are one of the most prominent characters of DS. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13258-020-00996-8) contains supplementary material, which is available to authorized users. * Xiaoling Jiang [email protected] 1
Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong 510623, China
2
Though the underlying mechanisms have not been fully understood, hippocamp
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