Transcriptome Analysis Identifies SenZfp536, a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors

Kuan Tian 1,2• Andi Wang 1,2• Junbao Wang 1,2• Wei Li 1,2• Wenchen Shen 1,2•Yamu Li 1,2
• Zhiyuan Luo 1,2• Ying Liu 1,2• Yan Zhou 1,2,3


1 College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430072, China
2 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
3 Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

Abstract

Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

Keywords

Zfp536 ; Sense lncRNA ; Self-renewal ; Cortical development  ;Neural progenitor

[SpringerLink]

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