Key result
Multiomics profiling reveals distinct pathways between valve cells and osteoblasts, identifying novel CAVD targets.
Why the study?
Understanding the proteomic and transcriptomic landscapes underlying osteogenic differentiation can unveil potential therapeutic targets for calcific aortic valve disease.
This multiomics study demonstrates that osteogenic differentiation in calcific aortic valve disease operates via distinct pathways compared to normal bone formation, highlighting novel therapeutic targets like MAOA and proving the superiority of DIA-based proteomics for primary cell cultures.
Answers are grounded in this paper and cite their sources.
These targets should not yet influence CAVD management; extends preclinical insights into valve versus bone differentiation pathways.
Osteogenic differentiation is crucial in normal bone formation and pathological calcification, such as calcific aortic valve disease (CAVD). Understanding the proteomic and transcriptomic landscapes underlying this differentiation can unveil potential therapeutic targets for CAVD. In this study, we employed RNA sequencing transcriptomics and proteomics on a timsTOF Pro platform to explore the multiomics profiles of valve interstitial cells (VICs) and osteoblasts during osteogenic differentiation. For proteomics, we utilized 3 data acquisition/analysis techniques: data-dependent acquisition (DDA)-parallel accumulation serial fragmentation (PASEF) and data-independent acquisition (DIA)-PASEF with a classic library-based (DIA) and machine learning-based library-free search (DIA-ML). Using RNA sequencing data as a biological reference, we compared these 3 analytical techniques in the context of actual biological experiments. We use this comprehensive dataset to reveal distinct proteomic and transcriptomic profiles between VICs and osteoblasts, highlighting specific biological processes in their osteogenic differentiation pathways. The study identified potential therapeutic targets specific for VICs osteogenic differentiation in CAVD, including the MAOA and ERK1/2 pathway. From a technical perspective, we found that DIA-based methods demonstrate even higher superiority against DDA for more sophisticated human primary cell cultures than it was shown before on HeLa samples. While the classic library-based DIA approach has proved to be a gold standard for shotgun proteomics research, the DIA-ML offers significant advantages with a relatively minor compromise in data reliability, making it the method of choice for routine proteomics.
No takes yet. Share an insight, caveat, or question.
Lobov et al. (2025) studied Calcific Aortic Valve Disease (CAVD) (n=11). Osteogenic differentiation vs. Standard cultivation was evaluated on Proteomic and transcriptomic profiles (differential expression). Multiomics profiling revealed distinct proteomic and transcriptomic pathways between valve interstitial cells and osteoblasts during osteogenic differentiation, identifying targets like MAOA and ERK1/2 for CAVD.
Synapse has enriched 10 related papers. Consider them for comparative context: