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Cross-Tissue Single-Nucleus RNA Sequencing Discovers Tissue-Resident Adipocytes Involved in Propanoate Metabolism in the Human Heart.
Das, Sankha Subhra; Kar, Asha; Rajkumar, Sandhya; Lee, Seung Hyuk T; Alvarez, Marcus; Pietiläinen, Kirsi H; Pajukanta, Päivi.
Afiliação
  • Das SS; Department of Human Genetics (S.S.D., A.K., S.R., S.H.T.L., M.A., P.P.), David Geffen School of Medicine at UCLA.
  • Kar A; Department of Human Genetics (S.S.D., A.K., S.R., S.H.T.L., M.A., P.P.), David Geffen School of Medicine at UCLA.
  • Rajkumar S; Department of Human Genetics (S.S.D., A.K., S.R., S.H.T.L., M.A., P.P.), David Geffen School of Medicine at UCLA.
  • Lee SHT; Department of Human Genetics (S.S.D., A.K., S.R., S.H.T.L., M.A., P.P.), David Geffen School of Medicine at UCLA.
  • Alvarez M; Department of Human Genetics (S.S.D., A.K., S.R., S.H.T.L., M.A., P.P.), David Geffen School of Medicine at UCLA.
  • Pietiläinen KH; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland (K.H.P.).
  • Pajukanta P; HealthyWeightHub, Abdominal Center, Helsinki University Hospital and University of Helsinki, Finland (K.H.P.).
Arterioscler Thromb Vasc Biol ; 43(10): 1788-1804, 2023 10.
Article em En | MEDLINE | ID: mdl-37409528
BACKGROUND: Adipocytes are crucial regulators of cardiovascular health. However, not much is known about gene expression profiles of adipocytes residing in nonfat cardiovascular tissues, their genetic regulation, and contribution to coronary artery disease. Here, we investigated whether and how the gene expression profiles of adipocytes in the subcutaneous adipose tissue differ from adipocytes residing in the heart. METHODS: We used single-nucleus RNA-sequencing data sets of subcutaneous adipose tissue and heart and performed in-depth analysis of tissue-resident adipocytes and their cell-cell interactions. RESULTS: We first discovered tissue-specific features of tissue-resident adipocytes, identified functional pathways involved in their tissue specificity, and found genes with cell type-specific expression enrichment in tissue-resident adipocytes. By following up these results, we discovered the propanoate metabolism pathway as a novel distinct characteristic of the heart-resident adipocytes and found a significant enrichment of coronary artery disease genome-wide association study risk variants among the right atrium-specific adipocyte marker genes. Our cell-cell communication analysis identified 22 specific heart adipocyte-associated ligand-receptor pairs and signaling pathways, including THBS (thrombospondin) and EPHA (ephrin type-A), further supporting the distinct tissue-resident role of heart adipocytes. Our results also suggest chamber-level coordination of heart adipocyte expression profiles as we observed a consistently larger number of adipocyte-associated ligand-receptor interactions and functional pathways in the atriums than ventricles. CONCLUSIONS: Overall, we introduce a new function and genetic link to coronary artery disease for the previously unexplored heart-resident adipocytes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propionatos / Doença da Artéria Coronariana Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propionatos / Doença da Artéria Coronariana Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2023 Tipo de documento: Article