Murine Aortic Valve Cell Heterogeneity at Birth.

Abstract

Background: Heart valve function requires a highly organized ECM (extracellular matrix) network that provides the necessary biomechanical properties needed to withstand pressure changes during each cardiac cycle. Lay down of the valve ECM begins during embryogenesis and continues throughout postnatal stages when it is remodeled into stratified layers and arranged according to blood flow. Alterations in this process can lead to dysfunction and, if left untreated, heart failure. Despite this, the mechanisms that establish structure-function relationships of the valve, particularly during postnatal maturation, are poorly understood.

Methods: To address this, single-cell transcriptomics was performed on murine aortic valve structures at postnatal day 1.

Results: Overall, 18 clusters of 7 diverse cell populations were identified, including a novel valve endothelial cell subpopulation unique to postnatal day 1 and 3 previously unappreciated valve interstitial cell subpopulations defined as primitive, remodeling, and bioactive. Additional lineage tracing of the primitive valve interstitial cell subpopulation in mice uncovered a temporal and spatial trajectory throughout postnatal maturation.

Conclusions: In summary, this work highlights the heterogeneity of cell types within the aortic valve structure at birth that contribute to establishing and maintaining structure and function throughout life.