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Heterogeneity of Natriuretic Peptide Expression in the Hearts of Mice and Humans using Single Cell Transcriptomics

  • Author(s): Toomu, Avinash
  • Advisor(s): King, Kevin
  • et al.
Abstract

The atrial natriuretic (ANP) and B-type natriuretic peptides (BNP) are important clinical diagnostic markers that, in recent years, have also been leveraged in a therapeutic angle. The release of these peptides is commonly thought to be stimulated by myocardial stretch, whether that be due to a pressure or volume overload. These peptides have several effects in the body, but the main ones involve diuresis and natriuresis at the kidneys, vasodilation, and an inhibition of the sympathetic nervous system. Bulk methods, such as quantitative PCR (qPCR) and bulk RNA-seq, have been able to identify the triggers for the transcription of the genes that encode for these peptides, Nppa and Nppb, in the setting of various cardiac injuries. Limitations of these methods involve not being able to identify who the producers of these peptides are in the injured myocardium, where they might be located, and how quickly the transcription of these genes begins in response to a stressor. Here, using single-cell RNA-seq, I analyze a combination of human and mouse cardiac tissue and identify a small subset of cardiomyocytes that seem to be responsible for professionally producing these peptides. These cardiomyocytes are located directly adjacent to the site of injury and are being robustly produced as soon as four hours following a cardiac injury.

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