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Published on: January 10, 2025
Mass Spectrometry Imaging-Based Single-Cell Lipidomics Profiles Metabolic Signatures of Heart Failure
Jie Ren1, Hao-Wen Li2,3, Liang Chen1
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medicine Science (CAMS) and Perking Union Medical College (PUMC), Beijing, 100037, P. R. China.
Insights
This study identifies unique lipid signatures in single heart failure (HF) cardiomyocytes using mass spectrometry imaging. These findings offer potential single-cell biomarkers for diagnosing HF and understanding its metabolic basis.
Area of Science:
- Cardiovascular Biology
- Metabolomics
- Biomarker Discovery
Background:
- Heart failure (HF) is a major global health concern with high mortality rates.
- Metabolic remodeling in cardiomyocytes is crucial for HF progression.
- Current metabolic analyses face limitations due to metabolite dynamics and the need for high-quality isolated cells.
Purpose of the Study:
- To profile the lipid landscape of individual cardiomyocytes from HF mouse models.
- To identify specific metabolic signatures associated with HF at the single-cell level.
- To understand the spatial distribution and functional relevance of these HF-associated metabolic signatures.
Main Methods:
- Direct isolation of high-quality cardiomyocytes from transgenic HF mouse biopsies.
- Lipid profiling of individual cardiomyocytes using time-of-flight secondary ion mass spectrometry with delayed extraction.
- Mass spectrometry imaging to visualize spatial distribution of metabolic signatures within single cells.
Main Results:
- Identification of distinct lipidomic signatures differentiating HF cardiomyocytes from control subjects.
- Discovery of potential single-cell biomarkers for HF detection.
- Association of identified signatures with lipoprotein metabolism, transmembrane transport, and signal transduction pathways.
Conclusions:
- Mass spectrometry imaging of single cardiomyocytes provides a powerful approach to study HF pathogenesis.
- The identified HF-associated lipid signatures offer insights into disease-specific metabolic alterations.
- This study advances the understanding of lipid metabolism in HF at the single-cell resolution.
Abstract:
Heart failure (HF), leading as one of the main causes of mortality, has become a serious public health issue with high prevalence around the world. Single cardiomyocyte (CM) metabolomics promises to revolutionize the understanding of HF pathogenesis since the metabolic remodeling in the human hearts plays a vital role in the disease progression. Unfortunately, current metabolic analysis is often limited by the dynamic features of metabolites and the critical needs for high-quality isolated CMs. Here, high-quality CMs were directly isolated from transgenic HF mice biopsies and further employed in the cellular metabolic analysis. The lipids landscape in individual CMs was profiled with a delayed extraction mode in time-of-flight secondary ion mass spectrometry. Specific metabolic signatures were identified to distinguish HF CMs from the control subjects, presenting as possible single-cell biomarkers. The spatial distributions of these signatures were imaged in single cells, and those were further found to be strongly associated with lipoprotein metabolism, transmembrane transport, and signal transduction. Taken together, we systematically studied the lipid metabolism of single CMs with a mass spectrometry imaging method, which directly benefited the identification of HF-associated signatures and a deeper understanding of HF-related metabolic pathways.
