PLX155916

GSE141136: A Stem Cell-Derived Endothelial Cell Model that Responds to Tobacco Smoke Like Primary Endothelial Cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

To clarify how smoking leads to heart attacks and stroke, we developed an endothelial cell model (iECs) generated from human induced Pluripotent Stem Cells (iPSC) and evaluated its responses to tobacco smoke. These iECs exhibited a uniform endothelial morphology, expressed markers PECAM1/CD31, VWF/von Willebrand Factor, and CDH5/VE-Cadherin, and exhibited tube formation and Acetyl-LDL uptake comparable to primary endothelial cells (EC). RNA sequencing (RNAseq) revealed a robust correlation coefficient between iECs and EC (R = 0.76), whereas gene responses to smoke were qualitatively nearly identical between iECs and primary ECs (R=0.86). Further analysis of transcriptional responses implicated eighteen transcription factors in regulating responses to smoke treatment, and identified gene sets regulated by each transcription factor, including oxidative stress, DNA damage/repair, ER stress, apoptosis, and cell cycle arrest. Assays for 42 cytokines in HUVEC cells and iECs identified 23 cytokines that responded dynamically to cigarette smoke. These cytokines and cellular stress response pathways describe endothelial responses for lymphocyte attachment, activation of coagulation and complement, lymphocyte growth factors, and inflammation and fibrosis; EC-initiated events that collectively lead to atherosclerosis. Thus, these studies validate the iEC model and identify transcriptional response networks by which ECs respond to tobacco smoke. Our results systematically trace how ECs use these response networks to regulate genes and pathways, and finally cytokine signals to other cells, to initiate the diverse processes that lead to atherosclerosis and cardiovascular disease. SOURCE: David,Lee,Gerhold (david.gerhold@nih.gov) - Toxicogenomics Laboratory NCATS/NIH