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Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

Author

Listed:
  • Yin Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Fang Yao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lipeng Wang

    (Peking University)

  • Zheng Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zongna Ren

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dandan Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Mingzhi Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Leng Han

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Shi-qiang Wang

    (Peking University)

  • Bingying Zhou

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Li Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon co-culture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.

Suggested Citation

  • Yin Wang & Fang Yao & Lipeng Wang & Zheng Li & Zongna Ren & Dandan Li & Mingzhi Zhang & Leng Han & Shi-qiang Wang & Bingying Zhou & Li Wang, 2020. "Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16204-w
    DOI: 10.1038/s41467-020-16204-w
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    Cited by:

    1. Sungjin Min & Suran Kim & Woo-Sup Sim & Yi Sun Choi & Hyebin Joo & Jae-Hyun Park & Su-Jin Lee & Hyeok Kim & Mi Jeong Lee & Inhea Jeong & Baofang Cui & Sung-Hyun Jo & Jin-Ju Kim & Seok Beom Hong & Yeon, 2024. "Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Ian Fernandes & Shunsuke Funakoshi & Homaira Hamidzada & Slava Epelman & Gordon Keller, 2023. "Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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