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Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo

Author

Listed:
  • Kelvin See

    (Genome Institute of Singapore)

  • Wilson L. W. Tan

    (Genome Institute of Singapore
    National University Health System, Centre for Translational Medicine)

  • Eng How Lim

    (Genome Institute of Singapore
    National University Health System, Centre for Translational Medicine)

  • Zenia Tiang

    (Genome Institute of Singapore
    National University Health System, Centre for Translational Medicine)

  • Li Ting Lee

    (Genome Institute of Singapore)

  • Peter Y. Q. Li

    (National University Health System, Centre for Translational Medicine)

  • Tuan D. A. Luu

    (National University Health System, Centre for Translational Medicine)

  • Matthew Ackers-Johnson

    (National University Health System, Centre for Translational Medicine)

  • Roger S. Foo

    (Genome Institute of Singapore
    National University Health System, Centre for Translational Medicine)

Abstract

Cardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian heart are few and pre-existing adult cardiomyocytes divide only at very low rates. Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity in the cardiomyocyte stress-response has never been explored. Here, we show by single nuclear RNA-sequencing of cardiomyocytes from both mouse and human failing, and non-failing adult hearts that sub-populations of cardiomyocytes upregulate cell cycle activators and inhibitors consequent to the stress-response in vivo. We characterize these subgroups by weighted gene co-expression network analysis and discover long intergenic non-coding RNAs (lincRNA) as key nodal regulators. KD of nodal lincRNAs affects expression levels of genes related to dedifferentiation and cell cycle, within the same gene regulatory network. Our study reveals that sub-populations of adult cardiomyocytes may have a unique endogenous potential for cardiac regeneration in vivo.

Suggested Citation

  • Kelvin See & Wilson L. W. Tan & Eng How Lim & Zenia Tiang & Li Ting Lee & Peter Y. Q. Li & Tuan D. A. Luu & Matthew Ackers-Johnson & Roger S. Foo, 2017. "Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00319-8
    DOI: 10.1038/s41467-017-00319-8
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    Cited by:

    1. Gayan I. Balasooriya & David L. Spector, 2022. "Allele-specific differential regulation of monoallelically expressed autosomal genes in the cardiac lineage," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Enrique Goñi & Aina Maria Mas & Jovanna Gonzalez & Amaya Abad & Marta Santisteban & Puri Fortes & Maite Huarte & Mikel Hernaez, 2024. "Uncovering functional lncRNAs by scRNA-seq with ELATUS," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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