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Diseases of the heart and the kidney, including heart failure and chronic kidney disease, can dramatically impair life expectancy and the quality of life of patients. The heart and kidney form a functional axis; therefore, functional impairment of 1 organ will inevitably affect the function of the other. Fibrosis represents the common final pathway of diseases of both organs, regardless of the disease entity. Thus, inhibition of fibrosis represents a promising therapeutic approach to treat diseases of both organs and to resolve functional impairment. However, despite the growing knowledge in this field, the exact pathomechanisms that drive fibrosis remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized the investigation of pathomechanisms at a molecular level and facilitated the discovery of disease-associated cell types and mechanisms. In this review, we give a brief overview over the evolution of RNA-sequencing techniques, summarize most recent insights into the pathogenesis of heart and kidney fibrosis, and discuss how transcriptomic data can be used, to identify new drug targets and to develop novel therapeutic strategies.

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants., Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8 + T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19., Results: We observed increased CD8 + T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8 + effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8 + T cells revealed heterogeneity among CD16 + NK-like CD8 + T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions., Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8 + effector T cells, ultimately resulting in the appearance of NK-like CD8 + T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8 + T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8 + T cells in COVID-19 severity., Competing Interests: Author JS-R declares funding from GSK and Sanofi and consultant fees from Travere Therapeutics, Owkin and Astex Pharmaceuticals unrelated to this study. Author SH has funding from Novo Nordisk. Author RK has grants from Travere Therapeutics, Galapagos, Chugai, and Novo Nordisk and is a consultant or received honoraria from Bayer, Pfizer, Novo Nordisk, Lilly-Pharma and Gruenenthal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schreibing, Hannani, Kim, Nagai, Ticconi, Fewings, Bleckwehl, Begemann, Torow, Kuppe, Kurth, Kranz, Frank, Anslinger, Ziegler, Kraus, Enczmann, Balz, Windhofer, Balfanz, Kurts, Marx, Marx, Dreher, Schneider, Saez-Rodriguez, Costa, Hayat and Kramann.)