RT Journal Article
SR Electronic
T1 Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.30.179952
DO 10.1101/2020.06.30.179952
A1 Thomas J. Cahill
A1 Xin Sun
A1 Christophe Ravaud
A1 Cristina Villa del Campo
A1 Konstantinos Klaourakis
A1 Irina-Elena Lupu
A1 Allegra M. Lord
A1 Cathy Browne
A1 Sten Eirik W. Jacobsen
A1 David R. Greaves
A1 David G. Jackson
A1 Sally A. Cowley
A1 William James
A1 Robin P. Choudhury
A1 Joaquim Miguel Vieira
A1 Paul R. Riley
YR 2020
UL http://biorxiv.org/content/early/2020/07/02/2020.06.30.179952.abstract
AB Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Summary statement Tissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development and function to remodel the vascular plexus.