Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta
- Weizmann Institute of Science, Israel
- Victor Chang Cardiac Research Institute, Australia
- Technion-Israel Institute of Technology, Israel
- Chinese Academy of Sciences, China
- The University of Washington, United States
- The University of Queensland, Australia
- 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
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Stereo-sequencing: 3D Transcriptome of the mouse embryo at gastrulationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE65924).
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Single Cell Expression Profiling Resolves the Transcriptional Programs of Early Mesoderm DiversificationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE74994).
Article and author information
Author details
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
- Kari Alitalo, University of Helsinki, Finland
Version history
- Received: August 26, 2016
- Accepted: March 6, 2017
- Accepted Manuscript published: March 8, 2017 (version 1)
- 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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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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