Related Experiment Video
Updated: Jul 13, 2025
08:43
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
19.6K
Single-Molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-Related
Dogukan Mizrak1, Yang Zhao2, Hao Feng1
1Department of Cardiac Surgery (D.M., H.F., J.M., Y.T., Z.S., B.Y., Y.E.C.), University of Michigan Medical Center, Ann Arbor.
Arteriosclerosis, Thrombosis, and Vascular Biology
|October 12, 2023
Summary
High-resolution imaging revealed a rare smooth muscle cell (SMC) subtype in human thoracic aortic aneurysm (TAA) that expresses CARTPT. This subtype is enriched in males and may contribute to aortic calcification.
Area of Science:
- Cardiovascular Biology
- Genomics
- Cell Biology
Background:
- Single-cell RNA-sequencing often loses spatial context in tissue analysis.
- Human thoracic aortic aneurysm (TAA) presents challenges for traditional cell dissociation methods.
- High-resolution single-cell transcriptome imaging offers a solution to preserve spatial information.
Purpose of the Study:
- To identify rare smooth muscle cell (SMC) subtypes in human TAA tissue.
- To investigate the spatial distribution and function of specific genes within TAA.
- To understand the role of CARTPT in TAA pathogenesis.
Main Methods:
- Single-molecule spatial distribution of transcripts for 140 genes in TAA samples.
- In vitro studies and tissue staining to analyze human CART prepropeptide (CARTPT) regulation.
- High-resolution transcriptome imaging of fresh-frozen human TAA and control tissues.
Main Results:
- A spatially distinct CARTPT-expressing SMC subtype was identified, enriched in male TAA samples.
- Human CART protein was enriched in male TAA tissue, with truncated CARTPT secretion observed.
- CARTPT overexpression induced an osteochondrogenic switch in aortic SMCs, promoting medial calcification.
Conclusions:
- Single-molecule imaging effectively identifies rare SMC subtypes in challenging tissues like the aorta.
- A novel CARTPT-expressing SMC subtype is associated with male TAA.
- Human CART signaling may drive aortic SMC osteochondrogenic differentiation and medial calcification.
