Details

Autor(en) / Beteiligte

• Decano, Julius L.
• Iwamoto, Yukio
• Goto, Shinji
• Lee, Janey Y.
• Matamalas, Joan T.
• Halu, Arda
• Blaser, Mark
• Lee, Lang Ho
• Pieper, Brett
• Chelvanambi, Sarvesh
• Silva-Nicolau, Jessica
• Bartoli-Leonard, Francesca
• Higashi, Hideyuki
• Shibata, Haruki
• Vyas, Payal
• Wang, Jianguo
• Gostjeva, Elena
• Body, Simon C.
• Singh, Sasha A.
• Aikawa, Masanori
• Aikawa, Elena

Titel

A disease-driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling

Ist Teil von

• Cell reports (Cambridge), 2022-04, Vol.39 (2), p.110685-110685, Article 110685

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Cellular heterogeneity of aortic valves complicates the mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease-driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided omic profiling, and network-based analysis, we characterize the DDP fingerprint as CD44highCD29+CD59+CD73+CD45low and discover potential key regulators of human CAVD. These DDP-VICs demonstrate multi-lineage differentiation and osteogenic properties. Temporal proteomic profiling of DDP-VICs identifies potential targets for therapy, including MAOA and CTHRC1. In vitro loss-of-function experiments confirm our targets. Such a stepwise strategy may be advantageous for therapeutic target discovery in other disease contexts. [Display omitted] •CD44highCD29+CD59+CD73+CD45low cells are disease-driving population (DDP) VICs in CAVD•DDP-VICs possess osteogenic differentiation properties•Single-cell analysis and proteomics identified CAVD targets like MAOA and CTHRC1•MAOA and CTHRC1 inhibition attenuate calcification in human aortic VICs Decano et al. characterize valvular interstitial cells (VICs) that are CD44highCD29+CD59+CD73+CD45low within human calcific valve disease (CAVD) as a disease-driver population (DDP) capable of osteogenic and procalcific differentiation. Phenotype-guided single-cell, multi-omic analysis identifies potential CAVD key regulators, such as MAOA and CTHRC1, validated through in vitro loss of function and histology.