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

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.

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Acknowledgements

We thank members of the Zhou lab for critical reading of the manuscript. This work was supported by grants from the National Key R&D Program of China (2018YFA0800700), the National Natural Science Foundation of China (31970770, 31970676, and 31671418), the Natural Science Foundation of Hubei Province, China (2018CFA016), Fundamental Research Funds for the Central Universities, the Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University (TFJC2018005) and State Key Laboratory Special Fund 2060204.

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Correspondence to Ying Liu or Yan Zhou.

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Tian, K., Wang, A., Wang, J. et al. Transcriptome Analysis Identifies SenZfp536, a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors. Neurosci. Bull. 37, 183–200 (2021). https://doi.org/10.1007/s12264-020-00607-2

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Keywords

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