This dataset contains bulk RNA-sequencing data generated to enable custom transcriptome assembly and to provide expression context for matched ribosome profiling in the discovery of lineage-retained neuroblastoma tumor antigens. RNA was sequenced from 183 neuroblastoma samples comprising cell lines, patient-derived tumor organoids, and primary patient tumors spanning the adrenergic (ADRN) and mesenchymal (MES) lineage states, with 101 samples prepared as rRNA-depleted (total RNA) libraries and 82 samples prepared as poly(A)-selected libraries. Libraries were sequenced paired-end (2x150 bp) on the Illumina NovaSeq 6000 platform. Raw data are provided as paired-end fastq.gz files.
Background: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmaco-epigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS. Results: We measured DNA methylation profiles before and after GH treatment (with a duration of ~18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration, and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMC) that were enriched in promoter regions, CpG islands and blood cell-type specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of "cell development", "neuron differentiation" and "developmental growth", and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway. Conclusion: Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.
