title: Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta.
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 factorNkx2.5marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiacNkx2.5lineage 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 ofNkx2.5in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transientNkx2.5expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role forNkx2.5in hemoangiogenic lineage specification and diversification.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Lyad
authors.identifier: http://orcid.org/0000-0002-3442-2952
authors.initials: L
authors.lastname: Zamir
authors.affiliation: Victor Chang Cardiac Research Institute, Sydney, Australia.
authors.forename: Reena
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elisha
authors.initials: E
authors.lastname: Nathan
authors.affiliation: Victor Chang Cardiac Research Institute, Sydney, Australia.
authors.forename: Ralph
authors.initials: R
authors.lastname: Patrick
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Yifa
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yfat
authors.initials: Y
authors.lastname: Yahalom-Ronen
authors.affiliation: Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Alaa A
authors.initials: AA
authors.lastname: Arraf
authors.affiliation: Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schultheiss
authors.affiliation: 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.
authors.forename: Shengbao
authors.initials: S
authors.lastname: Suo
authors.affiliation: 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.
authors.forename: Jing-Dong Jackie
authors.initials: JJ
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guangdun
authors.initials: G
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Naihe
authors.identifier: http://orcid.org/0000-0003-1509-6378
authors.initials: N
authors.lastname: Jing
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, The University of Washington, Seattle, United States.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Palpant
authors.affiliation: School of Medical Sciences, Sydney Medical School, The University of Sydney, Westmead, Australia.|Embryology Unit, Children's Medical Research Institute, Westmead, Australia.
authors.forename: Patrick Pl
authors.initials: PP
authors.lastname: Tam
authors.affiliation: 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.
authors.forename: Richard P
authors.identifier: http://orcid.org/0000-0002-9950-9792
authors.initials: RP
authors.lastname: Harvey
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eldad
authors.identifier: http://orcid.org/0000-0002-5212-9426
authors.initials: E
authors.lastname: Tzahor
mesh_terms: D000818:Animals; D001011:Aorta / Q000196:embryology*; D002642:Chick Embryo; D004699:Endocardium / Q000196:embryology*; D055018:Hemangioblasts / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5 / Q000378:metabolism*; D051379:Mice; D062211:Spatio-Temporal Analysis
chemical_list: D000072576:Homeobox Protein Nkx-2.5; C484469:Nkx2-5 protein, mouse
keywords: Nkx2.5; cardiogenesis; developmental biology; hemangioblasts; hemogenic endothelium; nkx2.5; stem cells