hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration

Jisheng Sun, Elizabeth A. Peterson, Xin Chen and Jinhu Wang ()
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Jisheng Sun: Emory University
Elizabeth A. Peterson: Emory University
Xin Chen: Emory University
Jinhu Wang: Emory University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Although several tissues and chemokines orchestrate coronary formation, the guidance cues for coronary growth remain unclear. Here, we profile the juvenile zebrafish epicardium during coronary vascularization and identify hapln1a+ cells enriched with vascular-regulating genes. hapln1a+ cells not only envelop vessels but also form linear structures ahead of coronary sprouts. Live-imaging demonstrates that coronary growth occurs along these pre-formed structures, with depletion of hapln1a+ cells blocking this growth. hapln1a+ cells also pre-lead coronary sprouts during regeneration and hapln1a+ cell loss inhibits revascularization. Further, we identify serpine1 expression in hapln1a+ cells adjacent to coronary sprouts, and serpine1 inhibition blocks vascularization and revascularization. Moreover, we observe the hapln1a substrate, hyaluronan, forming linear structures along and preceding coronary vessels. Depletion of hapln1a+ cells or serpine1 activity inhibition disrupts hyaluronan structure. Our studies reveal that hapln1a+ cells and serpine1 are required for coronary production by establishing a microenvironment to facilitate guided coronary growth.

Date: 2023
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DOI: 10.1038/s41467-023-39323-6

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