GSE163102
Global gene expression profiles of cellular response in human induced pluripotent stem cell-derived cardiomyocytes to CFZ treatment
Purpose: Evaluate the molecular changes associated with Cfz -induced cardiotoxicity Methods: RNA-Seq analysis was performed to analyze global transcriptome profiles of hiPSC-CMs treated with DMSO (Control group), 1 µM  Carfilzomib ( Cfz group). The Illumina TruSeq technology was used to prepare RNA-Seq libraries, and next-generation sequencing was done via an Illumina HiSeq 2000. RNA sequence reads were aligned to the human reference genome (GRCh38) using STAR v2.5. HTSeq v0.6.1 was used to count the read numbers mapped of each gene, and then Fragments Per Kilobase Million (FPKM) was calculated to estimate gene abundance. Differential expression analysis was performed using the DESeq2 R package (2_1.6.3). The resulting P-values were adjusted using the Benjamini and Hochberg's approach. As detected by RNA-Seq, some differential genes regulated by Cfz were significantly involved in cardiac contraction and extracellular matrix (ECM).   Among the top 10 up-regulated genes post Cfz treatment,most of thoese genes was related to the heat shock protein expression( HSPA1B,HSPA6,,HSPH1, BAG3). And among the top 10 down-regulated genes post Cfz treatment, some correlated to contraction and Extra cellular matrix ( ITG11, SLC9A3, TNN1) . Conclusion: Carfilzomib -induced alteration of hiPSC-CM transcriptomic profiles. Enhanced HSPs  and down regulate cardiac related contraction gene and extracellular matrix. Overall design: RNA-Seq analysis was performed to compare global gene expression profiles of hiPSC-CMs treated with DMSO, 1 µM Cfz, in triplicate.