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

Zamir, Lyad, Singh, Reena, Nathan, Elisha, Patrick, Ralph, Yifa, Oren, Yahalom-Ronen, Yfat, Arrafi, Alaa A., Schultheiss, Thomas M., Suo, Shengbao, Han, Jing-Dong Jackie, Peng, Guangdun, Jing, Naihe, Wang, Yuliang, Palpant, Nathan, Tam, Patrick P. L., Harveyz, Richard P. and Tzahor, Eldad (2017) Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta. ELife, 6 . doi:10.7554/eLife.20994


Author Zamir, Lyad
Singh, Reena
Nathan, Elisha
Patrick, Ralph
Yifa, Oren
Yahalom-Ronen, Yfat
Arrafi, Alaa A.
Schultheiss, Thomas M.
Suo, Shengbao
Han, Jing-Dong Jackie
Peng, Guangdun
Jing, Naihe
Wang, Yuliang
Palpant, Nathan
Tam, Patrick P. L.
Harveyz, Richard P.
Tzahor, Eldad
Title Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta
Journal name ELife   Check publisher's open access policy
ISSN 2050-084X
Publication date 2017-03-08
Sub-type Article (original research)
DOI 10.7554/eLife.20994
Open Access Status DOI
Volume 6
Total pages 31
Place of publication Cambridge, United Kingdom
Publisher ELife Sciences Publications
Language eng
Subject 2800 Neuroscience
1300 Biochemistry, Genetics and Molecular Biology
2400 Immunology and Microbiology
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/CD45and RUNX1cells 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.
Formatted 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.
Keyword Nkx2.5
cardiogenesis
developmental biology
hemangioblasts
hemogenic endothelium
nkx2.5
stem cells
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1074386
1110751
573705
573732
SR110001002
Institutional Status UQ

 
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