Hematopoietic progenitors are required for proper development of coronary vasculature

Gentian Lluri; Vincent Huang; Marlin Touma; Xiaoqian Liu; Andrew W Harmon; Atsushi Nakano

doi:10.1016/j.yjmcc.2015.07.021

Hematopoietic progenitors are required for proper development of coronary vasculature

J Mol Cell Cardiol. 2015 Sep:86:199-207. doi: 10.1016/j.yjmcc.2015.07.021. Epub 2015 Aug 1.

Authors

Gentian Lluri¹, Vincent Huang², Marlin Touma³, Xiaoqian Liu², Andrew W Harmon², Atsushi Nakano⁴

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, Section of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Children's Discovery and Innovation Institute Department of Pediatrics, Department of Molecular Cell and Integrative Physiology, David Geffen School of Medicine, USA.
⁴ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].

Abstract

Rationale: During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown.

Objective: Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature.

Methods and results: As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors.

Conclusion: Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.

Keywords: Cardiac development; Coronary formation; EMT; Epicardium; Hematopoietic progenitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics*
Cell Lineage / genetics
Core Binding Factor Alpha 2 Subunit / genetics
Coronary Vessels / embryology
Coronary Vessels / growth & development*
Coronary Vessels / metabolism
Embryo, Mammalian
Embryonic Development / genetics*
Epithelial-Mesenchymal Transition / genetics
Heart / growth & development*
Mice
Mice, Knockout

Substances

Core Binding Factor Alpha 2 Subunit
Runx1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding