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Single Cell Transcriptomics of In Vitro and In Vivo bone marrow Nrf2-stimulated macrophages and Pro-inflammatory SiglecFHigh neutrophils

  • Author(s): Huang, Kenneth Mark
  • Advisor(s): King, Kevin
  • et al.
No data is associated with this publication.
Abstract

Myocardial infarction (MI) is the leading cause of death in the U.S., affecting elderly populations and more recently, younger populations. Treatments thus far have reduced rates of myocardial infarction (MI), but progress has slowed due to downstream consequences of heart failure, especially involving the immune system response to necrotic cells in the heart, causing subsequent inflammation. To elucidate gene expression and specialized subsets of immune cells that exacerbate or ameliorate inflammation after MI we have analyzed the single-cell transcriptomics of mice bone marrow, the source of inflammation of the heart. We have observed differences in single-cell gene expression between bone marrow in vitro and in vivo of mice four days post-MI, especially in the expression of cardioprotective and proliferative macrophages, marked by genes such as Top2a and Mki67, in vitro. Additionally, we compared single-cell transcriptomic differences of in vitro bone marrow derived macrophages with in vivo bone marrow macrophages. We have also found specialized neutrophils, SiglecFHigh neutrophils, that are suggested to exacerbate inflammation in the heart via the IL6 pathway. Lastly, we reported crosstalk between the IRF3 pathway and the Nrf2 pathway, especially between itaconate, a key Nrf2 component and interferon-beta (IFN-B), a component of the IRF3 pathway. In conclusion, single cell revealed new populations of specialized immune cells that can potentially aid or detriment post-MI recovery. Further investigation into specialized immune cells using in vivo imaging and functional characterization of neutrophils will allow for higher resolution of immune cell function and potential antibody-based therapeutics designed to reduce SiglecFHigh neutrophils.

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This item is under embargo until June 24, 2023.