PLX313525

GSE156340: Dynamic changes in RNA-chromatin interactome promote endothelial dysfunction (RNA-seq)

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

Chromatin-associated RNA has been proposed as a type of epigenomic modification. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high-glucose and TNF (H+T), that mimic the common stress in diabetes mellitus. We characterize the H+T induced changes of single-cell RNA expression by scRNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H+T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H+T induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate with H+T induced RNA-chromatin interactions. These data highlight RNA-chromatin interactions as a regulatory feature to endothelial dysfunction, a major mediator of numerous diseases. SOURCE: Sheng Zhong (szhong@eng.ucsd.edu) - University of California San Diego