Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2017 Sep 12

PMID 28890073

Citations 55

Authors

Bikram Sharma

Lena Ho

Gretchen Hazel Ford

Heidi I Chen

Andrew B Goldstone

Y Joseph Woo

Thomas Quertermous

Bruno Reversade

Kristy Red-Horse

Affiliations

Soon will be listed here.

Abstract

Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function. An upregulation of endocardial SOX17 accompanied compensation in Apj mutants, which was also seen in Ccbe1 knockouts, indicating that the endocardium is activated in multiple cases where sinus venosus angiogenesis is stunted. Our data demonstrate that by diversifying their responsivity to growth cues, distinct coronary progenitor pools are able to compensate for each other during coronary development, thereby providing robustness to organ development.

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References

Das S, Red-Horse K . Cellular plasticity in cardiovascular development and disease. Dev Dyn. 2017; 246(4):328-335. PMC: 5489309. DOI: 10.1002/dvdy.24486. View

Wu B, Zhang Z, Lui W, Chen X, Wang Y, Chamberlain A . Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling. Cell. 2012; 151(5):1083-96. PMC: 3508471. DOI: 10.1016/j.cell.2012.10.023. View

Del Toro R, Prahst C, Mathivet T, Siegfried G, Kaminker J, Larrivee B . Identification and functional analysis of endothelial tip cell-enriched genes. Blood. 2010; 116(19):4025-33. PMC: 4314527. DOI: 10.1182/blood-2010-02-270819. View

Ho L, van Dijk M, Chye S, Messerschmidt D, Chng S, Ong S . ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. Science. 2017; 357(6352):707-713. DOI: 10.1126/science.aam6607. View

Claveria C, Giovinazzo G, Sierra R, Torres M . Myc-driven endogenous cell competition in the early mammalian embryo. Nature. 2013; 500(7460):39-44. DOI: 10.1038/nature12389. View

Deshwar A, Chng S, Ho L, Reversade B, Scott I . The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development. Elife. 2016; 5. PMC: 4859801. DOI: 10.7554/eLife.13758. View

Perez-Camps M, Tian J, Chng S, Sem K, Sudhaharan T, Teh C . Quantitative imaging reveals real-time Pou5f3-Nanog complexes driving dorsoventral mesendoderm patterning in zebrafish. Elife. 2016; 5. PMC: 5042653. DOI: 10.7554/eLife.11475. View

Bui H, Enis D, Robciuc M, Nurmi H, Cohen J, Chen M . Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD. J Clin Invest. 2016; 126(6):2167-80. PMC: 4887177. DOI: 10.1172/JCI83967. View

Bos F, Caunt M, Peterson-Maduro J, Planas-Paz L, Kowalski J, Karpanen T . CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ Res. 2011; 109(5):486-91. DOI: 10.1161/CIRCRESAHA.111.250738. View

10.

Meyer S, Amoyel M, Bergantinos C, de la Cova C, Schertel C, Basler K . An ancient defense system eliminates unfit cells from developing tissues during cell competition. Science. 2014; 346(6214):1258236. PMC: 5095928. DOI: 10.1126/science.1258236. View

11.

Tian X, Hu T, Zhang H, He L, Huang X, Liu Q . Vessel formation. De novo formation of a distinct coronary vascular population in neonatal heart. Science. 2014; 345(6192):90-4. PMC: 4275002. DOI: 10.1126/science.1251487. View

12.

Bort R, Signore M, Tremblay K, Martinez Barbera J, Zaret K . Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev Biol. 2005; 290(1):44-56. DOI: 10.1016/j.ydbio.2005.11.006. View

13.

Tian X, Hu T, Zhang H, He L, Huang X, Liu Q . Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries. Cell Res. 2013; 23(9):1075-90. PMC: 3760626. DOI: 10.1038/cr.2013.83. View

14.

van den Akker N, Caolo V, Wisse L, Peters P, Poelmann R, Carmeliet P . Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. Cardiovasc Res. 2007; 78(2):366-75. DOI: 10.1093/cvr/cvm108. View

15.

Yu F, Zhao B, Guan K . Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell. 2015; 163(4):811-28. PMC: 4638384. DOI: 10.1016/j.cell.2015.10.044. View

16.

Inui M, Fukui A, Ito Y, Asashima M . Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis. Dev Biol. 2006; 298(1):188-200. DOI: 10.1016/j.ydbio.2006.06.028. View

17.

Yang P, Maguire J, Davenport A . Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system. Trends Pharmacol Sci. 2015; 36(9):560-7. PMC: 4577653. DOI: 10.1016/j.tips.2015.06.002. View

18.

Yzaguirre A, Padmanabhan A, de Groh E, Engleka K, Li J, Speck N . Loss of neurofibromin Ras-GAP activity enhances the formation of cardiac blood islands in murine embryos. Elife. 2015; 4:e07780. PMC: 4714971. DOI: 10.7554/eLife.07780. View

19.

de Beco S, Ziosi M, Johnston L . New frontiers in cell competition. Dev Dyn. 2012; 241(5):831-41. PMC: 3440443. DOI: 10.1002/dvdy.23783. View

20.

Zhang H, Pu W, Li G, Huang X, He L, Tian X . Endocardium Minimally Contributes to Coronary Endothelium in the Embryonic Ventricular Free Walls. Circ Res. 2016; 118(12):1880-93. DOI: 10.1161/CIRCRESAHA.116.308749. View