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Comparative analysis of the down syndrome hippocampal non-coding RNA transcriptomes using a mouse model

Genes & Genomics 2020년 42권 11호 p.1259 ~ 1265
Cai Zhaowei, Xiao Zhilan, Wang Yufang, Liu Huazhen, Zhang Kangdi, Zhen Xiaoning, Jiang Xiaoling,
소속 상세정보
 ( Cai Zhaowei ) - Zhejiang Chinese Medical University Laboratory Animal Research Center
 ( Xiao Zhilan ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology
 ( Wang Yufang ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology
 ( Liu Huazhen ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology
 ( Zhang Kangdi ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology
 ( Zhen Xiaoning ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology
 ( Jiang Xiaoling ) - Guangzhou Medical University Guangzhou Women and Children’s Medical Center Department of Genetics and Endocrinology

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-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.

키워드

Down syndrome; Transcriptome; Hippocampus; microRNA; lncRNA; Circular RNA

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