The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH45229, USA.
Laboratory of Cardiology, GIGA Cardiovascular Sciences, University of Liège, CHU Sart Tilman, Liège 4000, Belgium.
Development. 2019 Mar 12;146(12):dev173047. doi: 10.1242/dev.173047.
Heart valve cells mediate extracellular matrix (ECM) remodeling during postnatal valve leaflet stratification, but phenotypic and transcriptional diversity of valve cells in development is largely unknown. Single cell analysis of mouse heart valve cells was used to evaluate cell heterogeneity during postnatal ECM remodeling and leaflet morphogenesis. The transcriptomic analysis of single cells from postnatal day (P)7 and P30 murine aortic (AoV) and mitral (MV) heart valves uncovered distinct subsets of melanocytes, immune and endothelial cells present at P7 and P30. By contrast, interstitial cell populations are different from P7 to P30. P7 valve leaflets exhibit two distinct collagen- and glycosaminoglycan-expressing interstitial cell clusters, and prevalent ECM gene expression. At P30, four interstitial cell clusters are apparent with leaflet specificity and differential expression of complement factors, ECM proteins and osteogenic genes. This initial transcriptomic analysis of postnatal heart valves at single cell resolution demonstrates that subpopulations of endothelial and immune cells are relatively constant throughout postnatal development, but interstitial cell subpopulations undergo changes in gene expression and cellular functions in primordial and mature valves.
心脏瓣膜细胞在出生后瓣膜小叶分层过程中介导细胞外基质 (ECM) 的重塑，但在发育过程中瓣膜细胞的表型和转录多样性在很大程度上尚不清楚。利用小鼠心脏瓣膜细胞的单细胞分析来评估出生后 ECM 重塑和小叶形态发生过程中的细胞异质性。对来自出生后第 7 天 (P7) 和第 30 天 (P30) 的小鼠主动脉 (AoV) 和二尖瓣 (MV) 心脏瓣膜的单个细胞的转录组分析揭示了 P7 和 P30 时存在的黑素细胞、免疫细胞和内皮细胞的不同亚群。相比之下，间质细胞群在 P7 到 P30 期间有所不同。P7 瓣膜小叶表现出两个具有明显特征的胶原蛋白和糖胺聚糖表达的间质细胞簇，以及普遍的 ECM 基因表达。在 P30，有四个间质细胞簇，具有小叶特异性和补体因子、ECM 蛋白和成骨基因的差异表达。这项对出生后心脏瓣膜单细胞分辨率的初始转录组分析表明，内皮细胞和免疫细胞的亚群在整个出生后发育过程中相对稳定，但间质细胞亚群的基因表达和细胞功能在原始和成熟瓣膜中发生变化。
