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B03 - Hypertension and metabolic stress associated changes in cardiac cell populations

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Project summary

Normal function of the human heart relies on highly heterogeneous cell populations with specialized functions. In response to systemic stress and/or injury, reparative processes such as fibrosis occur contributing to adverse remodeling and promoting mechanical dysfunction, arrhythmias and heart failure. To obtain insights into trigger-response patterns in HFpEF, we will apply single-nucleus RNA-sequencing (snRNA-seq) to study the composition of cardiac cell populations in biopsies of HFpEF patients and murine models of diastolic dysfunction. We will characterize cardiac cell states and types, their expression networks and cellular circuits, and locate these in space. By comparing changes between non-failing hearts and HFpEF we will discern fundamental causes of maladaptive cardiac remodeling, characterize heterogeneous cellular responses and infer new therapeutic strategies.

 

Graphical Abstract: We will apply single cell technologies to define the cellular and molecular definition of disease associated changes between healthy and diseased hearts. In addition, with our spatial analysis we aim to define the regional architecture of cardiac cell types and states in HFpEF hearts. Our comparative analyses of cardiac cell populations will be accomplished by gene expression measurements and analysis of chromatin organization between  clinical and preclinical HFpEF phenogroups.

Team

Additional group members

PhD students: Anna Myronova

Postdoc: Henrike Maatz

 

 

 

 


Publications

Ercu M, Mücke MB, Pallien T, Markó L, Sholokh A, Schächterle C, Aydin A, Kidd A, Walter S, Esmati Y, McMurray BJ, Lato DF, Yumi Sunaga-Franze D, Dierks PH, Flores BIM, Walker-Gray R, Gong M, Merticariu C, Zühlke K, Russwurm M, Liu T, Batolomaeus TUP, Pautz S, Schelenz S, Taube M, Napieczynska H, Heuser A, Eichhorst J, Lehmann M, Miller DC, Diecke S, Qadri F, Popova E, Langanki R, Movsesian MA, Herberg FW, Forslund SK, Müller DN, Borodina T, Maass PG, Bähring S, Hübner N, Bader M, Klussmann E. Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage. Circulation. 2022 Dec 6;146(23):1758-1778. doi: 10.1161/CIRCULATIONAHA.122.060210. Epub 2022 Oct 19. PMID: 36259389.

Reichart D, Lindberg EL, Maatz H, Miranda AMA, Viveiros A, Shvetsov N, Gärtner A, Nadelmann ER, Lee M, Kanemaru K, Ruiz-Orera J, Strohmenger V, DeLaughter DM, Patone G, Zhang H, Woehler A, Lippert C, Kim Y, Adami E, Gorham JM, Barnett SN, Brown K, Buchan RJ, Chowdhury RA, Constantinou C, Cranley J, Felkin LE, Fox H, Ghauri A, Gummert J, Kanda M, Li R, Mach L, McDonough B, Samari S, Shahriaran F, Yapp C, Stanasiuk C, Theotokis PI, Theis FJ, van den Bogaerdt A, Wakimoto H, Ware JS, Worth CL, Barton PJR, Lee YA, Teichmann SA, Milting H, Noseda M, Oudit GY, Heinig M, Seidman JG, Hubner N, Seidman CE. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science. 2022 Aug 5;377(6606):eabo1984. doi: 10.1126/science.abo1984. Epub 2022 Aug 5. PMID: 35926050; PMCID: PMC9528698.