Medical Clinic and Polyclinic I
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Single cell genomics

Cardiac tissue consists of several different cell types such as cardiomyocytes, fibroblasts or macrophages. This cellular diversity is required for normal cardiac contractility, relaxation and excitability. Single cell techniques extract cell type-specific information by measuring the transcriptome of each cardiac cell type, which helps to decipher the genetic information of healthy and diseased hearts. This technique enables the analysis of compositional changes and heterogeneity within each cell type and state (= cell subtypes). ScRNA-seq using droplet-based microfluidics combines high throughput, good sensitivity and broad applicability. However, due to their cell size of 100 x 25 μm, adult cardiac myocytes are not compatible with droplet-based microfluidic scRNA-seq techniques. Since the average diameter of their cell nuclei is 8-12 μm, single-nucleus RNA sequencing (snRNA-seq) of cardiac tissue offers a robust alternative to scRNA-seq and captures data from all cardiac lineages - even from frozen tissue.

LMU Klinikum

The 11 most important cell types and representative marker genes of the adult human heart are shown in a two-dimensional representation using the 'Uniform Manifold Approximation and Projection' (UMAP). Each dot represents a detected nucleus. Modified from Nature, 588, pp. 466-72 (2020).

Gene editing

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

LMU Klinikum

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

Originally translated with DeepL