Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta

  1. Lyad Zamir
  2. Reena Singh
  3. Elisha Nathan
  4. Ralph Patrick
  5. Oren Yifa
  6. Yfat Yahalom-Ronen
  7. Alaa A Arraf
  8. Thomas M Schultheiss
  9. Shengbao Suo
  10. Jing-Dong Jackie Han
  11. Guangdun Peng
  12. Naihe Jing
  13. Yuliang Wang
  14. Nathan Palpant
  15. Patrick PL Tam
  16. Richard P Harvey  Is a corresponding author
  17. Eldad Tzahor  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Victor Chang Cardiac Research Institute, Australia
  3. Technion-Israel Institute of Technology, Israel
  4. Chinese Academy of Sciences, China
  5. The University of Washington, United States
  6. The University of Queensland, Australia
  7. The University of Sydney, Australia

Abstract

Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac Nkx2.5 lineage progenitors migrate into the embryo and contribute to clusters of CD41+/CD45+ and RUNX1+ cells in the endocardium, the aorta-gonad-mesonephros region of the dorsal aorta and liver. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient Nkx2.5 expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for Nkx2.5 in hemoangiogenic lineage specification and diversification.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Lyad Zamir

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Reena Singh

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Elisha Nathan

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Ralph Patrick

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Oren Yifa

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Yfat Yahalom-Ronen

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Alaa A Arraf

    Department of Genetics and Developmental Biology, Technion-Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Thomas M Schultheiss

    Department of Genetics and Developmental Biology, Technion-Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Shengbao Suo

    Key Laboratory of Computational Biology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Jing-Dong Jackie Han

    Key Laboratory of Computational Biology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Guangdun Peng

    State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Naihe Jing

    State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1509-6378
  13. Yuliang Wang

    Institute for Stem Cell and Regenerative Medicine, The University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Nathan Palpant

    Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Patrick PL Tam

    Embryology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Richard P Harvey

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    For correspondence
    r.harvey@victorchang.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  17. Eldad Tzahor

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    eldad.tzahor@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5212-9426

Funding

Israel Science Foundation

  • Lyad Zamir
  • Elisha Nathan
  • Oren Yifa
  • Eldad Tzahor

National Health and Medical Research Council (1074386,573732,1110751)

  • Reena Singh
  • Ralph Patrick
  • Patrick PL Tam
  • Richard P Harvey

Stem Cells Australia (SR110001002)

  • Reena Singh
  • Ralph Patrick
  • Richard P Harvey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mice used in this study were bred and maintained in the Victor Chang Cardiac Research Institute BioCore facility according to the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes.Use of chick embryos before embryonic Day 21 does not require IACUC approval.

Reviewing Editor

  1. Kari Alitalo, University of Helsinki, Finland

Publication history

  1. Received: August 26, 2016
  2. Accepted: March 6, 2017
  3. Accepted Manuscript published: March 8, 2017 (version 1)
  4. Version of Record published: April 21, 2017 (version 2)

Copyright

© 2017, Zamir et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lyad Zamir
  2. Reena Singh
  3. Elisha Nathan
  4. Ralph Patrick
  5. Oren Yifa
  6. Yfat Yahalom-Ronen
  7. Alaa A Arraf
  8. Thomas M Schultheiss
  9. Shengbao Suo
  10. Jing-Dong Jackie Han
  11. Guangdun Peng
  12. Naihe Jing
  13. Yuliang Wang
  14. Nathan Palpant
  15. Patrick PL Tam
  16. Richard P Harvey
  17. Eldad Tzahor
(2017)
Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta
eLife 6:e20994.
https://doi.org/10.7554/eLife.20994
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