单细胞转录组测序揭示了糖尿病诱导的心肌细胞代谢变化和微环境变化。

IF 2.6 4区 生物学 Q2 BIOLOGY Computational Biology and Chemistry Pub Date : 2024-06-21 DOI:10.1016/j.compbiolchem.2024.108136
Weiyu Zhou, Haiqiao Yu, Shuang Yan
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引用次数: 0

摘要

目的:糖尿病是一种以血糖水平升高为特征的慢性代谢性疾病。本研究旨在分析糖尿病(DM)中 CMs 的异质性和通讯特性的基本变化:GSE213337 数据集来自 NCBI 基因表达总库,包含对照组和链脲佐菌素诱导的糖尿病小鼠心脏的单细胞 RNA 测序数据。利用GSEA和GSVA探讨了DEGs在CM中的功能富集。通过细胞通讯分析研究了改变的信号和重要的配体-受体相互作用:结果:在 DM 和对照组中发现了 17 种细胞类型。结果:DM和对照组之间共发现了17种细胞类型,CM比例的增加表明糖尿病的发生诱发了CM增殖的潜在病理变化。在 CM 中共鉴定出 1144 个 DEGs。GSEA和GSVA分析表明,DM患者的脂质代谢增强。细胞通讯分析结果表明,高糖激活了CM接受成纤维细胞和LEC的能力,而抑制了接受ECC和周细胞的能力。此外,在DM条件下,GAS和ANGPTL明显下降,这与GSEA和GSVA的结果一致。最后,CM中的配体-受体相互作用,如vegfc-vegfr2、angptl1发生了变化:结论:CM在DM中表现出明显的异质性,在高血糖诱导的心肌纤维化中起着重要作用。
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Single-cell transcriptome sequencing revealed the metabolic changes and microenvironment changes of cardiomyocytes induced by diabetes

Purpose

Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels. This study aimed to analyze the changes underlying heterogeneities and communication properties of CMs in diabetes mellitus (DM).

Methods

GSE213337 dataset was retrieved from NCBI Gene Expression Omnibus, containing the single-cell RNA sequencing data of hearts from the control and streptozotocin-induced diabetic mice. GSEA and GSVA were used to explore the function enrichment of DEGs in CM. Cell communication analysis was carried out to study the altered signals and significant ligand-receptor interactions.

Results

Seventeen cell types were identified between DM and the controls. The increasing ratio of CM suggested the occurrence of diabetes induces potential pathological changes of CM proliferation. A total of 1144 DEGs were identified in CM. GSEA and GSVA analysis indicated the enhancing lipid metabolism involving in DM. The results of cell communication analysis suggested that high glucose activated the ability of CM receiving fibroblast and LEC, while inhibited the capacity of receiving ECC and pericyte. Furthermore, GAS and ANGPTL were significantly decreased under DM, which was consistent with the results of GSEA and GSVA. Finally, the ligand-receptor interactions such as vegfc-vegfr2, angptl1 were changes in CM.

Conclusions

The CM showed the significant heterogeneities in DM, which played an important role in myocardial fibrosis induce by hyperglycemia.

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来源期刊
Computational Biology and Chemistry
Computational Biology and Chemistry 生物-计算机:跨学科应用
CiteScore
6.10
自引率
3.20%
发文量
142
审稿时长
24 days
期刊介绍: Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.
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