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Single-nucleus profiling of the left ventricle of the mouse heart after chronic stress
Yaping Li1, Xia Liu1, Huaxing Zhang2
1College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identifications, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province, 050017, China.
Insights
Chronic stress impacts heart health, but mechanisms remain unclear. This study maps left ventricle cells using single-nucleus RNA sequencing to identify stress-induced cardiac injury biomarkers.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Stress Physiology
Background:
- The link between stress and cardiac disease is established, yet precise mechanisms and diagnostic indicators for stress-induced cardiac injury are lacking.
- Chronic stress is implicated in sudden cardiac death, but cellular responses and regulatory pathways in the left ventricle remain poorly understood.
- Understanding cellular heterogeneity in the left ventricle under chronic stress is crucial for cardiovascular disease research.
Purpose of the Study:
- To create a comprehensive cellular atlas of the left ventricle under chronic stress conditions.
- To identify molecular mechanisms underlying cardiovascular dysfunction caused by chronic stress.
- To discover potential biomarkers for diagnosing and treating stress-related cardiac injury.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) was employed to profile cellular populations.
- A dataset of 99,154 left ventricle cells was generated, comprising 42,491 from stressed samples and 56,663 from controls.
- All major cardiac cell types within the left ventricle were comprehensively analyzed.
Main Results:
- A detailed cellular atlas of the left ventricle under chronic stress was successfully established.
- The study provides a foundation for understanding the molecular basis of chronic stress effects on cardiovascular health.
- Key cellular differences and potential biomarkers associated with stress-induced cardiac dysfunction were identified.
Conclusions:
- The established cellular atlas offers critical insights into the molecular mechanisms of chronic stress on the left ventricle.
- This research paves the way for developing novel diagnostic tools and therapeutic strategies for stress-related cardiovascular diseases.
- Identifying cellular heterogeneity is key to understanding and addressing stress-induced cardiac injury.
Abstract:
It is widely accepted that stress and cardiac disease are related, but the exact mechanism is still up for debate. Although stress has been scientifically confirmed as a causative factor, there is still a lack of qualitative and quantitative indicator systems for stress-induced cardiac injury. The forensic evidence frequently indicates that cases of sudden cardiac death are often preceded by prolonged exposure to chronic stress factors. However, the cellular responses and mechanisms that trigger and regulate these activities in the pathological and physiological processes of chronic stress are still poorly understood. The left ventricle (LV), as a critical target organ in cardiovascular diseases, still has unclear cellular heterogeneity under chronic stress. Using single-nucleus RNA sequencing (snRNA-seq), we established a cellular atlas of 99,154 LV cells (42,491 stress and 56,663 control), comprehensively profiling all major cardiac cell types. The resulting dataset not only provides a foundation for deciphering the molecular mechanisms underlying chronic stress in cardiovascular dysfunction but also enables the identification of potential biomarkers for future diagnostic and therapeutic strategies.
