Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Reena Singh
Victor Chang Cardiac Research Institute, Sydney, Australia
Elisha Nathan
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Ralph Patrick
Victor Chang Cardiac Research Institute, Sydney, Australia
Oren Yifa
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Yfat Yahalom-Ronen
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Alaa A Arraf
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Thomas M Schultheiss
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Shengbao Suo
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Jing-Dong Jackie Han
Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Guangdun Peng
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Yuliang Wang
Institute for Stem Cell and Regenerative Medicine, The University of Washington, Seattle, United States
Nathan Palpant
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
Patrick PL Tam
School of Medical Sciences, Sydney Medical School, The University of Sydney, Westmead, Australia; Embryology Unit, Children’s Medical Research Institute, Westmead, Australia
Victor Chang Cardiac Research Institute, Sydney, Australia; St. Vincent’s Clinical School, School of Biological and Biomolecular Sciences, University of New South Wales, Kensington, Australia
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.
