Transcriptomics,Genomics

Dataset Information

161

Analysis of Combined Transcriptomes Identifies Gene Modules Differentially Responding to Pathogenic Stimulation in Vascular Smooth Muscle and Endothelial Cells


ABSTRACT: Smooth muscle cells (SMCs) and endothelial cells (ECs) constitute vasculature media and endothelium, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but also damage the protective endothelial lining, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMCs versus ECs) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFα or IL-1β, both established inducers of SMC hyperplasia and EC dysfunction. To analyze combined SMC/EC transcriptomes we developed customized algorithms. Induced by TNFα or IL-1β, 212 and 263 genes respectively showed greater up-regulation in SMCs than in ECs (SMC-enriched), while 140 and 204 genes showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene interaction networks identified 5 common hubs and 4 common bottlenecks in the two SMC-enriched gene sets, and 8 hubs and 3 bottlenecks shared in the EC-enriched gene sets. Significantly, four gene modules were formed with these hubs and bottlenecks. While the JUN module (including JUN, KLF5, HIF1A, CXCL8, FOSL1) and FYN module (FYN, JAK2, MAP2, PIK3R3, DAB2, ASAP2) were SMC-enriched, the SMAD3 (SMAD3, CDKN1A, TRAF1, BCL6, CEBPD, TRIB3, ANK3) and XPO1 (XPO1, ETS2, SSH2, NDRG1, GFPT2?) modules were EC-enriched. As these core subnetworks respond to pathogenic stimulation in a SMC-versus-EC differential manner, they may inform potential intervention targets for selective mitigation of SMC hyperplasia without endothelial damage. Overall design: In this study, we performed RNA sequencing (RNA-seq) and global analyses of differential SMC-versus-EC transcriptomic responses, to the same pathogenic cytokine stimulant under stringently controlled conditions. The objective was to identify the gene modules (or subnetworks) that are highly up-regulated in SMCs yet little affected or regulated toward the opposite direction in ECs

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Lianwang Guo  

PROVIDER: GSE96962 | GEO | 2018-02-14

REPOSITORIES: GEO

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Publications

Analysis of Combined Transcriptomes Identifies Gene Modules that Differentially Respond to Pathogenic Stimulation of Vascular Smooth Muscle and Endothelial Cells.

Pan Xiaokang X   Wang Bowen B   Yuan Tiezheng T   Zhang Mengxue M   Kent K Craig KC   Guo Lian-Wang LW  

Scientific reports 20180110 1


Smooth muscle cells (SMCs) and endothelial cells (ECs) are vital cell types composing the vascular medial wall and the atheroprotective inner lining, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but compromise EC integrity, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMC versus EC) disease-associated regulations remain poorly defined. We conducted RNA-seq expe  ...[more]

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