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Mesenchymal (MES)- and Adrenergic (ADN) neuroblastoma cell line pair of isogenic origin

ABSTRACT: Mesenchymal (MES)- and Adrenergic (ADN) neuroblastoma cell line pair of isogenic origin

PROVIDER: PRJNA515056 | ENA |

REPOSITORIES: ENA

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Mesenchymal (MES)- and Adrenergic (ADN) neuroblastoma cell line pair of isogenic origin

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ASCL1: a pioneer factor that induces subtype switching and characterizes adrenergic neuroblastoma

Project description:Neuroblastoma is an embryonic malignancy originating from early nerve cells. Neuroblastoma retains plasticity, interconverting between the mesenchymal (MES) and adrenergic (ADRN) states, which are controlled by different sets of transcription factors forming the core regulatory circuit (CRC). However, their functional roles and cooperative mechanisms in neuroblastoma pathogenesis are poorly understood. Here, we demonstrate that overexpression of ASCL1 in MES neuroblastoma cells opens closed chromatin at the promoters of key ADRN genes, accompanied by epigenetic activation and establishment of enhancer-promoter interactions, thereby initiating subtype switching. ASCL1 inhibits the TGFb-SMAD2/3 pathway but activates the BMP-SMAD1-ID3/4 pathway, serving as negative feedback to balance the function of ASCL1-TCF12 dimers. ASCL1 and other ADRN CRC members potentiate each other’s activity, increasing the expression of the original targets and inducing a new set of genes, thereby promoting conversion to ADRN neuroblastoma. Thus, via its pioneer factor function, ASCL1 serves as a master regulator that characterizes ADRN neuroblastoma.

2023-12-08 | PXD037670 | Pride

A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.

Project description:Transition between differentiation states in development occurs swift but the mechanisms leading to epigenetic and transcriptional reprogramming are poorly understood. The pediatric cancer neuroblastoma includes adrenergic (ADRN) and mesenchymal (MES) tumor cell types, which differ in phenotype, super-enhancers (SEs) and core regulatory circuitries. These cell types can spontaneously interconvert, but the mechanism remains largely unknown. Here, we unravel how a NOTCH3 intracellular domain reprogrammed the ADRN transcriptional landscape towards a MES state. A transcriptional feed-forward circuitry of NOTCH-family transcription factors amplifies the NOTCH signaling levels, explaining the swift transition between two semi-stable cellular states. This transition induces genome-wide remodeling of the H3K27ac landscape and a switch from ADRN SEs to MES SEs. Once established, the NOTCH feed-forward loop maintains the induced MES state. In vivo reprogramming of ADRN cells shows that MES and ADRN cells are equally oncogenic. Our results elucidate a swift transdifferentiation between two semi-stable epigenetic cellular states.

2019-04-18 | GSE129980 | GEO

mES phosphoproteome data - mES phosphoproteome data

Project description:mES phosphoproteome data

2010-12-17 | PRD000256 | Pride

mes-2, mes-4 or mes-2; mes-4 mutants vs. wild type

2012-05-30 | GSE38158 | GEO

Transcript and chromatin analysis in mes-2, mes-4, and mes-2; mes-4 double mutants

Project description:This SuperSeries is composed of the following subset Series: GSE38158: mes-2, mes-4 or mes-2; mes-4 mutants vs. wild type GSE38159: Strome MES-4, H3K36me3 and H3K27me3 in mes-4 RNAi EEMB GSE38180: Strome Mes-4, H3K36me3 and H3K27me3 in N2 EEMB Refer to individual Series

2012-05-29 | E-GEOD-38160 | biostudies-arrayexpress

mes-2, mes-4 or mes-2; mes-4 mutants vs. wild type

Project description:Trascriptional profiling of C. elegans adult germ lines comparing mes-2(bn11)unc-4(e120) mutants and unc-4(e120) (wild type), mes-4(bn85) mutants and N2 (wild type), mes-2(bn11)unc-4(e120); mes-4(bn85) and unc-4(e120) (wild type) at 20 degrees. One-condition experiment, mutant vs. WT. Biological replicates 4 mutant, 4 wildtype harvested indepedently. One mutant replicate and one WT replicate per array.

2012-05-29 | E-GEOD-38158 | biostudies-arrayexpress

Resequencing of a pair of chickpea near-isogenic lines with contrasting flowering time.

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