GSE173610
Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC) -derived sensory neurons - RNA-Seq data on transcriptional changes induced by 1µM paclitaxel treatment for 24h
We report data on transcriptome sequencing analyses of functional iPSC-DSN (maturation >d40) treated with 1 µM paclitaxel for 24h compared to DMSO treatment. RNA-Sequencing analyses revealed 319 significantly differentially (padjusted <0.01) expressed genes out of which 227 were upregulated and 92 downregulated. 84 of the upregulated and 33 of the downregulated changed expression by at least 2 fold. Upregulated genes involve known neuronal injury markers such as the Activation Transcription Factor (ATF3), stress-inducible proteins such as Sestrin-2 (SESN2), apoptosis associated genes such as Caspase 3 (CASP3), the JUN proto-oncogene (JUN) or BCL2-interacting proteins such as BBC3 or Harakiri (HRK). Also, vasoactive substances and pain inducing neuropeptides of the calcitonine gene related peptide family such as CALCB and adrenomedullin (ADM) were found amongst the top 50 differentially regulated genes. Downregulated genes involve pathways of sterol homeostasis, glucose homeostasis and  lipogenesis, e.g., 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Insulin Induced Gene 1 (INSIG1) or ELOVL Fatty Acid Elongase 6 (ELOVL6). Gene set enrichment analysis outlined significant deregulation of genes involved in cholesterol biosynthesis pathways, PERK regulated genes and genes involved in amino acid transport across the membrane. In summary, there is a significant overlap of the above mentioned genes and gene sets outlined by unbiased global differential transcriptome analyses with pathways known from the literature of neuropathy and neurodegeneration. Overall design: 3 replicates of iPSC-DSN of the cell line BIHi005-A were treated with DMSO 1/6000 and 2 with with 1 µM paclitaxel.