Effect of depletion of LEMD3 on gene expression of A7r5 vascular smooth muscle cells [RNA-seq]

The contractile phenotype of vascular smooth muscle cells is essential for maintaining vascular homeostasis.In this study, we found that LEMD3, a nuclear membrane protein, may be involved in maintaining the contractile phenotype of vascular smooth muscle cells through a genome-scale CRISPR screen. Mechanistically, we combined RNA-seq with ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to find out differentially expressed genes and altered chromatin accessibility. By overlapping down-regulated genes and genes located in less accessible chromatin regions, we identified 143 genes including VSMCs contractile genes such as Acta2, Cnn1, Tagln, and key transcription factor Srf, suggesting that LEMD3 maintains VSMCs contractile phenotype by regulating chromatin accessibility.血管平滑肌细胞（vascular smooth muscle cells，以下简称VSMCs）的收缩表型对于维持血管稳态至关重要。本研究通过全基因组CRISPR筛选发现，核膜蛋白LEMD3可能参与维持VSMCs的收缩表型。机制层面，我们联合运用RNA-seq与ATAC-seq（Assay for Transposase-Accessible Chromatin using sequencing）分析差异表达基因与染色质可及性变化情况。通过对下调基因与染色质可及性降低区域的基因取交集，我们鉴定得到143个基因，其中包括Acta2、Cnn1、Tagln等VSMCs收缩相关基因以及关键转录因子Srf，这表明LEMD3通过调控染色质可及性维持VSMCs的收缩表型。