Single cell profiling of adipose tissue in atherosclerosis
| Autor: | U Thanigai Arasu, T Ord, J Liikkanen, S Kettunen, T Lonnberg, S Palani, S Yla-Herttuala, A Roivainen, MU Kaikkonen |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Cardiovascular Research. 118 |
| ISSN: | 1755-3245 0008-6363 |
| Popis: | Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Academy of Finland Sigrid Jusélius Foundation Adipose tissue influences the physiological and pathological processes in our body by regulating lipid storage and metabolic homeostasis. Extracellular matrix (ECM) is a dynamic and complex assemblage consisting of polysaccharides, proteogylcans and signalling proteins. Though both adipocytes and non- adipose cells of the stromal fraction contribute to ECM maintenance, role of adipose tissue ECM in the disease remains poorly characterised. High fat diet (HFD) and obesity represent major risk factors for atherosclerosis. Our overall aim in this study was to understand HFD induced changes in the adipose tissue during atherosclerosis progression using single cell RNA sequencing (scRNA-seq), to identify the ligands responsible for changes in the expression of ECM components and to characterise the role of ECM protein fibrillin in disease associated tissue changes. We performed scRNA-seq in the adipose tissue of control mice and atherosclerotic LDLR-/- / ApoB100/100 subjected to 1 (early disease) or 3 months (advanced disease) of HFD. This allowed us to identify 13 different cell types in the adipose tissue of the diseased mice. Among them, we identified mesenchymal cells (MSC) undergoing changes from putatively adipogenic to fibrogenic cells. The differentially expressed genes in the MSC population exhibited functions related to ECM development, maintenance and signalling. We identified Fibrillin-1 (Fbn1) as one of the most prominent up regulated genes and studied the effect of Fbn1 knockout in ApoE-/- Fbn1C1039G+/- mice. The Fbn1 knockout mice model suited our experimental design to study the adipose tissue during atherosclerosis as the mice developed significantly large and unstable plaques characterised by large necrotic core. Our results demonstrated that adipose tissue expresses a new subtype with HFD in Fbn1 knockout mice, which could be associated with insulin resistance and fat accumulation. Fbn1 knockout led to an altered phenotype of MSCs (or adipocytes) in adipose tissue. Altogether, our analysis provides the first steps toward understanding the role of MSCs in ECM-related changes during atherosclerosis and HFD stimulation. |
| Databáze: | OpenAIRE |
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