Single-Cell Transcriptomics Identifies Selective Lineage-Specific Regulation of Genes in Aortic Smooth Muscle Cells...

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Genomics

Background:

• Smooth muscle cells (SMCs) in the proximal thoracic aorta originate from the second heart field (SHF) and cardiac neural crest (CNC).
• Lineage-specific SMC functions are implicated in thoracic aortic diseases.
• Transcriptional differences between SHF- and CNC-derived SMCs in the healthy aorta are largely unexplored.

Purpose of the Study:

• To investigate potential transcriptomic differences between SHF-derived and CNC-derived SMCs in the control aorta.
• To identify specific genes that are differentially expressed between these two SMC lineages.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) and single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) were performed on mouse aortic cells.
• Cells were isolated from SHF-traced and CNC-traced male mice.
• RNA in situ hybridization was used to validate gene expression patterns.

Main Results:

• scRNA-seq identified 12 upregulated differentially expressed genes (DEGs) in SHF-SMCs and 9 in CNC-SMCs.
• A distinct subpopulation of SHF-SMCs showed enrichment for Des and Tnnt2 expression.
• snATAC-seq confirmed greater chromosomal accessibility for upregulated DEGs in SHF-SMCs.

Conclusions:

• Limited but distinct transcriptomic differences exist between CNC-derived and SHF-derived SMCs in the proximal thoracic aorta.
• These findings provide a baseline understanding of lineage-specific SMC characteristics.
• Further research is warranted to explore the functional implications of these transcriptomic variations.