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Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

ABSTRACT: Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

SUBMITTER: Kim S

PROVIDER: S-EPMC10607172 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Kim Seongmin S Noh Ji Heon JH Lee Min Ji MJ Park Ye Jin YJ Kim Bo Mi BM Kim Yun-Seok YS Hwang Sangik S Park Chungoo C Kim Kyuseok K

International journal of molecular sciences 20231018 20

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobia ...[more]

PMID: 37895006

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Project description:Sepsis is a life-threatening condition with multi-organ failure caused by a dysregulated host response to infection. Among different organs susceptible to infection, the lung is the main one leading to sepsis 4. Patients with severe sepsis are at a high risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which occurs in up to 50% of patients. Myeloid C-type lectin domain family 5 member A (CLEC5A) is a pattern recognition receptor that participates in host defense against infection. Blockage of CLEC5A increased survival of mice with polymicrobial sepsis or endotoxemia, and protected the lungs against septic infection. To explore the underlying cellular and molecular mechanisms of CLEC5A in sepsis-induced lung injury, a comprehensive single-cell transcriptomics of CLEC5A-/- lungs was generated by scRNA-seq. Mice were subjected to cecal ligation and puncture (CLP), and the lungs were collected 12 h post-surgery. Single cell suspensions were prepared from lung tissues of three CLEC5A-/- mice and three WT littermates, and pooled cells from these mice were subjected to scRNA-seq processing using the 10×Genomics Chromium system. A total of 55,177 single cells, including 29,306 cells from WT lungs and 15,871 cells from CLEC5A-/- lungs, were obtained after removal of multiplets and filtration of low-quality cells. Total cells were grouped into 34 distinct clusters by Uniform Manifold Approximation and Projection, and a total of 14 distinct cell types were identified, including granulocytes, T cells, B cells, alveolar-macrophages (AM), monocytes, macrophages, natural killer T cells (NKT), mesothelium, natural killer cells (NK), endothelial cells, fibroblasts, dendritic cells (DC), epithelial cells, and smooth muscle cells (SMC).The scRNA-seq analysis implied the potential role of CLEC5A in endothelial cells regarding crosstalk with immune cells in septic lungs. Deletion of CLEC5A inhibited endothelial barrier dysfunction induced by sepsis, and decreased leukocyte-endothelial adhesion and transendothelial migration. The role of CLEC5A in pulmonary endothelial cells and the barrier function is identified for the first time, which contributes to the regulation of immunity/inflammation in the lungs under septic infection. This work extends the therapeutic potential of targeting CLEC5A in sepsis-induced endothelial barrier dysfunction and lung injury.

Dataset Information

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Publications

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

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