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Epigenetic landscape reveals MECOM as an endothelial lineage regulator

Author

Listed:
  • Jie Lv

    (Houston Methodist Research Institute)

  • Shu Meng

    (Houston Methodist Research Institute)

  • Qilin Gu

    (Houston Methodist Research Institute)

  • Rongbin Zheng

    (Boston Children’s Hospital
    Harvard Medical School)

  • Xinlei Gao

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Jun-dae Kim

    (Houston Methodist Research Institute)

  • Min Chen

    (Boston Children’s Hospital
    Harvard Medical School)

  • Bo Xia

    (Houston Methodist Research Institute)

  • Yihan Zuo

    (Boston Children’s Hospital
    Harvard Medical School)

  • Sen Zhu

    (Houston Methodist Research Institute)

  • Dongyu Zhao

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Yanqiang Li

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Guangyu Wang

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Xin Wang

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Qingshu Meng

    (Northwestern University Feinberg School of Medicine
    Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine)

  • Qi Cao

    (Northwestern University Feinberg School of Medicine
    Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine)

  • John P. Cooke

    (Houston Methodist Research Institute)

  • Longhou Fang

    (Houston Methodist Research Institute)

  • Kaifu Chen

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Lili Zhang

    (Houston Methodist Research Institute
    Boston Children’s Hospital
    Harvard Medical School)

Abstract

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator.

Suggested Citation

  • Jie Lv & Shu Meng & Qilin Gu & Rongbin Zheng & Xinlei Gao & Jun-dae Kim & Min Chen & Bo Xia & Yihan Zuo & Sen Zhu & Dongyu Zhao & Yanqiang Li & Guangyu Wang & Xin Wang & Qingshu Meng & Qi Cao & John P, 2023. "Epigenetic landscape reveals MECOM as an endothelial lineage regulator," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38002-w
    DOI: 10.1038/s41467-023-38002-w
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    References listed on IDEAS

    as
    1. Jason Ernst & Pouya Kheradpour & Tarjei S. Mikkelsen & Noam Shoresh & Lucas D. Ward & Charles B. Epstein & Xiaolan Zhang & Li Wang & Robbyn Issner & Michael Coyne & Manching Ku & Timothy Durham & Mano, 2011. "Mapping and analysis of chromatin state dynamics in nine human cell types," Nature, Nature, vol. 473(7345), pages 43-49, May.
    2. Bo Xia & Dongyu Zhao & Guangyu Wang & Min Zhang & Jie Lv & Alin S. Tomoiaga & Yanqiang Li & Xin Wang & Shu Meng & John P. Cooke & Qi Cao & Lili Zhang & Kaifu Chen, 2020. "Machine learning uncovers cell identity regulator by histone code," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Elisabetta Dejana & Karen K. Hirschi & Michael Simons, 2017. "The molecular basis of endothelial cell plasticity," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    4. Robert E. Thurman & Eric Rynes & Richard Humbert & Jeff Vierstra & Matthew T. Maurano & Eric Haugen & Nathan C. Sheffield & Andrew B. Stergachis & Hao Wang & Benjamin Vernot & Kavita Garg & Sam John &, 2012. "The accessible chromatin landscape of the human genome," Nature, Nature, vol. 489(7414), pages 75-82, September.
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