Murine aortic valve cell heterogeneity at birth

Abstract

Heart valve function requires a highly organized extracellular matrix (ECM) 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. To address this, single cell transcriptomics was performed on murine aortic valve structures at postnatal day one (PND1). Overall, 18 clusters of 7 diverse cell populations were identified, including a novel VEC subpopulation unique to PND1, and three previously unappreciated VIC subpopulations defined as "primitive", "remodeling" and "bioactive". Additional lineage tracing of the "primitive" VIC subpopulation in mice uncovered a temporal and spatial trajectory throughout postnatal maturation. 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.