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Single-cell analysis of early progenitor cells that build coronary arteries

Author

Listed:
  • Tianying Su

    (Stanford University)

  • Geoff Stanley

    (Stanford University)

  • Rahul Sinha

    (Stanford University School of Medicine)

  • Gaetano D’Amato

    (Stanford University)

  • Soumya Das

    (Stanford University)

  • Siyeon Rhee

    (Stanford University)

  • Andrew H. Chang

    (Stanford University)

  • Aruna Poduri

    (Stanford University)

  • Brian Raftrey

    (Stanford University)

  • Thanh Theresa Dinh

    (Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
    Stanford University)

  • Walter A. Roper

    (Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
    Stanford University)

  • Guang Li

    (Stanford University School of Medicine)

  • Kelsey E. Quinn

    (University of North Carolina at Chapel Hill)

  • Kathleen M. Caron

    (University of North Carolina at Chapel Hill)

  • Sean Wu

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Lucile Miquerol

    (Aix-Marseille Université)

  • Eugene C. Butcher

    (Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
    Stanford University)

  • Irving Weissman

    (Stanford University School of Medicine)

  • Stephen Quake

    (Stanford University
    Chan Zuckerberg Biohub)

  • Kristy Red-Horse

    (Stanford University)

Abstract

Arteries and veins are specified by antagonistic transcriptional programs. However, during development and regeneration, new arteries can arise from pre-existing veins through a poorly understood process of cell fate conversion. Here, using single-cell RNA sequencing and mouse genetics, we show that vein cells of the developing heart undergo an early cell fate switch to create a pre-artery population that subsequently builds coronary arteries. Vein cells underwent a gradual and simultaneous switch from venous to arterial fate before a subset of cells crossed a transcriptional threshold into the pre-artery state. Before the onset of coronary blood flow, pre-artery cells appeared in the immature vessel plexus, expressed mature artery markers, and decreased cell cycling. The vein-specifying transcription factor COUP-TF2 (also known as NR2F2) prevented plexus cells from overcoming the pre-artery threshold by inducing cell cycle genes. Thus, vein-derived coronary arteries are built by pre-artery cells that can differentiate independently of blood flow upon the release of inhibition mediated by COUP-TF2 and cell cycle factors.

Suggested Citation

  • Tianying Su & Geoff Stanley & Rahul Sinha & Gaetano D’Amato & Soumya Das & Siyeon Rhee & Andrew H. Chang & Aruna Poduri & Brian Raftrey & Thanh Theresa Dinh & Walter A. Roper & Guang Li & Kelsey E. Qu, 2018. "Single-cell analysis of early progenitor cells that build coronary arteries," Nature, Nature, vol. 559(7714), pages 356-362, July.
  • Handle: RePEc:nat:nature:v:559:y:2018:i:7714:d:10.1038_s41586-018-0288-7
    DOI: 10.1038/s41586-018-0288-7
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    Cited by:

    1. Gregory Farber & Yanhan Dong & Qiaozi Wang & Mitesh Rathod & Haofei Wang & Michelle Dixit & Benjamin Keepers & Yifang Xie & Kendall Butz & William J. Polacheck & Jiandong Liu & Li Qian, 2024. "Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Ki Oh & Yun Jae Yoo & Luke A. Torre-Healy & Manisha Rao & Danielle Fassler & Pei Wang & Michael Caponegro & Mei Gao & Joseph Kim & Aaron Sasson & Georgios Georgakis & Scott Powers & Richard A. Moffitt, 2023. "Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Francisco X. Galdos & Sidra Xu & William R. Goodyer & Lauren Duan & Yuhsin V. Huang & Soah Lee & Han Zhu & Carissa Lee & Nicholas Wei & Daniel Lee & Sean M. Wu, 2022. "devCellPy is a machine learning-enabled pipeline for automated annotation of complex multilayered single-cell transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Susanne Fleig & Tamar Kapanadze & Jeremiah Bernier-Latmani & Julia K. Lill & Tania Wyss & Jaba Gamrekelashvili & Dustin Kijas & Bin Liu & Anne M. Hüsing & Esther Bovay & Adan Chari Jirmo & Stephan Hal, 2022. "Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Sarasa Isobe & Ramesh V. Nair & Helen Y. Kang & Lingli Wang & Jan-Renier Moonen & Tsutomu Shinohara & Aiqin Cao & Shalina Taylor & Shoichiro Otsuki & David P. Marciano & Rebecca L. Harper & Mir S. Adi, 2023. "Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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