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Series GSE90683 Query DataSets for GSE90683
Status Public on Jul 01, 2017
Title Heterogeneity of neuroblastoma cell identity revealed by transcriptional circuitries
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define Core Regulatory Circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 family TFs; a mixed type further deconvoluted at the single cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a novel aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.
 
Overall design ChIP-seq data for neuroblastoma cell lines (H3K27ac, GATA3, HAND2, PHOX2B) and hNCC cell lines (H3K27ac); RNA-seq for neuroblastoma cell lines and hNCC cell lines.
Raw sequence data for the PDX Samples have been deposited at the EBI's European Genome-phenome Archive (EGA).
 
Contributor(s) Valentina B, Isabelle J
Citation(s) 28740262
Submission date Nov 30, 2016
Last update date May 15, 2019
Contact name Valentina Boeva
Organization name Institut Cochin
Department Inserm U1016
Street address 24 rue du Faubourg Saint-Jacques
City Paris
ZIP/Postal code 75014
Country France
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (101)
GSM2664313 CLB-BER-Lud H3K27ac, ChIP-seq
GSM2664314 CLB-BER-Lud Input, ChIP-seq
GSM2664315 CLB-CAR H3K27ac, ChIP-seq
Relations
BioProject PRJNA355381
SRA SRP094096

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE90683_Log2FPKMExpressionSummary.txt.gz 6.6 Mb (ftp)(http) TXT
GSE90683_RAW.tar 2.2 Gb (http)(custom) TAR (of BED, BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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