Medizinische Klinik und Poliklinik I
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  2. Medizinische Klinik und Poliklinik I
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AG Reichart/Lindberg

  • Single-cell genomics

    The heart tissue is composed of multiple different cell types such as cardiomyocytes, fibroblasts or macrophages. This cellular diversity is necessary for normal heart contractility, relaxation and excitability. Single cell techniques extract cell type-specific information by measuring the transcriptome of each cardiac cell type, which helps to unravel the genetic readouts from healthy and diseased hearts. This technique enables the dissection of compositional changes and heterogeneity within each cell type and -state (=cell subtypes). ScRNA-seq using droplet-based microfluidic combines high-throughput, good sensitivity, and wide applicability. However due to their cell size of 100x25μm, adult CMs are not compatible with droplet-based microfluidics scRNA-seq techniques. As the average diameter of CM nuclei is 8-12μm, single nucleus RNA sequencing (snRNA-seq) of heart tissue provides a robust alternative to scRNA-seq and captures data from all cardiac lineages – even from frozen tissues.

    LMU Klinikum

    The 11 major cell types and representative marker genes of the adult human heart are depicted in a 2-dimensional representation using the Uniform Manifold Approximation and Projection, (UMAP). Each dot represents one captured nucleus. Modified from Nature, 588, p 466–72 (2020).

    Gene editing

    Nucleic acid therapies are potential therapeutic approaches for cardiovascular genetic diseases. DNA modification can be achieved with genome editors delivered by vectors like adeno-associated viruses or liponanoparticles. CRISPR-based tools such as base or prime editing allow – even in post-mitotic cells – precise and efficient genome editing enabling modification of monogenetic cardiovascular diseases.

    LMU Klinikum

    Three different types of CRISPR-based tools: nucleases, base and prime editors. Modified from Nature Biotechnology, 38, pages 824–44 (2020)