Ravindran et al. 2024 (PRJNA935940)

General Details

Title Smooth muscle cell-specific translatome profiling of mouse atherosclerosis uncovers Itih4 as a novel SMC-enriched gene
Organism
Number of Samples 18
Release Date 2023/02/16 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP423221
ENA SRP423221
GEO GSE225424
BioProject PRJNA935940

Publication

Title
Authors Ravindran A,Holappa L,Niskanen H,Skovorodkin I,Kaisto S,Beter M,Kiema M,Selvarajan I,Nurminen V,Aavik E,Aherrahrou R,Pasonen-Seppänen S,Fortino V,Laakkonen JP,Ylä-Herttuala S,Vainio S,Örd T,Kaikkonen MU
Journal Cardiovascular research
Publication Date 2024 Jul 2
Abstract Vascular smooth muscle cells (SMCs) and their derivatives are key contributors to the development of atherosclerosis. However, studying changes in SMC gene expression in heterogeneous vascular tissues is challenging due to the technical limitations and high cost associated with current approaches. In this paper, we apply translating ribosome affinity purification sequencing to profile SMC-specific gene expression directly from tissue. To facilitate SMC-specific translatome analysis, we generated SMCTRAP mice, a transgenic mouse line expressing enhanced green fluorescent protein (EGFP)-tagged ribosomal protein L10a (EGFP-L10a) under the control of the SMC-specific αSMA promoter. These mice were further crossed with the atherosclerosis model Ldlr-/-, ApoB100/100 to generate SMCTRAP-AS mice and used to profile atherosclerosis-associated SMCs in thoracic aorta samples of 15-month-old SMCTRAP and SMCTRAP-AS mice. Our analysis of SMCTRAP-AS mice showed that EGFP-L10a expression was localized to SMCs in various tissues, including the aortic wall and plaque. The TRAP fraction demonstrated high enrichment of known SMC-specific genes, confirming the specificity of our approach. We identified several genes, including Cemip, Lum, Mfge8, Spp1, and Serpina3, which are known to be involved in atherosclerosis-induced gene expression. Moreover, we identified several novel genes not previously linked to SMCs in atherosclerosis, such as Anxa4, Cd276, inter-alpha-trypsin inhibitor-4 (Itih4), Myof, Pcdh11x, Rab31, Serpinb6b, Slc35e4, Slc8a3, and Spink5. Among them, we confirmed the SMC-specific expression of Itih4 in atherosclerotic lesions using immunofluorescence staining of mouse aortic roots and spatial transcriptomics of human carotid arteries. Furthermore, our more detailed analysis of Itih4 showed its link to coronary artery disease through the colocalization of genome-wide association studies, splice quantitative trait loci (QTL), and protein QTL signals. We generated a SMC-specific TRAP mouse line to study atherosclerosis and identified Itih4 as a novel SMC-expressed gene in atherosclerotic plaques, warranting further investigation of its putative function in extracellular matrix stability and genetic evidence of causality. © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
PMC PMC11218691
PMID 38289873
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR24072173 PRJNA935940 Mus musculus
SRR24072171 PRJNA935940 Mus musculus
SRR24072169 PRJNA935940 Mus musculus
SRR24072167 PRJNA935940 Mus musculus
SRR24072165 PRJNA935940 Mus musculus
SRR24072163 PRJNA935940 Mus musculus
SRR24072161 PRJNA935940 Mus musculus
SRR24072159 PRJNA935940 Mus musculus
SRR24072157 PRJNA935940 Mus musculus
SRR24072155 PRJNA935940 Mus musculus
SRR24072153 PRJNA935940 Mus musculus
SRR24072151 PRJNA935940 Mus musculus
SRR24072149 PRJNA935940 Mus musculus
SRR24072147 PRJNA935940 Mus musculus
SRR24072145 PRJNA935940 Mus musculus
SRR24072143 PRJNA935940 Mus musculus
SRR24072141 PRJNA935940 Mus musculus
SRR24072139 PRJNA935940 Mus musculus
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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