Transcriptome Analysis Identifies SenZfp536 , a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors
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ORIGINAL ARTICLE
Transcriptome Analysis Identifies SenZfp536, a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors Kuan Tian1,2 • Andi Wang1,2 • Junbao Wang1,2 • Wei Li1,2 • Wenchen Shen1,2 Yamu Li1,2 • Zhiyuan Luo1,2 • Ying Liu1,2 • Yan Zhou1,2,3
•
Received: 28 November 2019 / Accepted: 12 August 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
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 Kuan Tian and Andi Wang have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00607-2) contains supplementary material, which is available to authorized users. & Ying Liu [email protected] & Yan Zhou [email protected] 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
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
Introduction The mammalian cerebral cortex, also known as the neocortex, is a six-layer structure comprising a large cohort of neurons and glial cells, which is the basis for sophisticated cognitive functions. Cortical projection neurons (PNs) are functional units that make long-distance connections with other parts of the central nervous system. Cortical PNs in mouse and human are generated directly and indirectly from radial glial progenitor cells (RGs), including apical and basal RGs, lying in the dorsal part of the embryonic forebrain [1, 2]. Some
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