A Cell Atlas of Thoracic Aortic Perivascular Adipose Tissue: a focus on mechanotransducers

  • bioRxiv. 2023 Oct 9:2023.10.09.561581. doi: 10.1101/2023.10.09.561581.
Janice M Thompson  1  2 ,  Stephanie W Watts  1  2 ,  Leah Terrian  3  2 ,  G Andres Contreras  4 ,  Cheryl Rockwell  1 ,  C Javier Rendon  4 ,  Emma Wabel  1 ,  Lizabeth Lockwood  1 ,  Sudin Bhattacharya  3  1  5  6 ,  Rance Nault  7  6  2  8
Affiliations
  • 1. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
  • 2. Denotes individuals contributed equally as first authors to this work.
  • 3. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA.
  • 4. Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
  • 5. Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
  • 6. Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
  • 7. Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, USA.
  • 8. Denotes lead contact.
PMID: 37873456 DOI: 10.1101/2023.10.09.561581
Abstract

Perivascular adipose tissue (PVAT) is increasingly recognized for its function in mechanotransduction. To examine the cell-specificity of recognized mechanotransducers we used single nuclei RNA Sequencing (snRNAseq) of the thoracic aorta PVAT (taPVAT) from male Dahl SS rats compared to subscapular brown adipose tissue (BAT). Approximately 30,000 nuclei from taPVAT and BAT each were characterized by snRNAseq, identifying 8 major cell types expected and one unexpected (nuclei with oligodendrocyte marker genes). Cell-specific differential gene expression analysis between taPVAT and BAT identified up to 511 genes (adipocytes) with many (≥20%) being unique to individual cell types. Piezo1 was the most highly, widely expressed mechanotransducer. Presence of PIEZO1 in the PVAT was confirmed by RNAscope® and IHC; antagonism of PIEZO1 impaired the PVAT's ability to hold tension. Collectively, the cell compositions of taPVAT and BAT are highly similar, and PIEZO1 is likely a mechanotransducer in taPVAT.

Keywords
Dahl SS rat; Perivascular adipose tissue; Piezo1; brown adipose tissue; mechanotransduction; single-nuclei RNA sequencing.
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