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Array comparative genomic hybridization of spheres derived from TH-MYCN (hemizygote) mice [Agilent-027441]

ABSTRACT: It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice, a neuroblastoma model. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In order to investigate the chromosomal alterations (gains or losses) of spheres derived from TH-MYCN mice, we carried out array comparative genomic hybridization. We investigated whether chromosomal alterations occured during early neuroblastoma tumorigenesis in TH-MYCN mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE89740 | GEO | 2017/04/01

SECONDARY ACCESSION(S): PRJNA353068

REPOSITORIES: GEO

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MYCN-transformed neuroblasts from TH-MYCN mice are selectively isolated and maintained as spheres in vitro

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In the present study, in order to investigate the transcriptomic differences among 3-week-old WT SMG, TH-MYCN (hemizygote) SMG, and TH-MYCN (hemizygote) spheres, we carried out microarray gene expression analysis. We investigated whether or not undifferentiated cells observed in TH-MYCN SMG were selectively isolated and maintaned as spheres.

2017-04-01 | GSE87782 | GEO

Transcriptomic changes in MYC and PRC2 targets are prominent events in the early pathogenesis of neuroblastoma in TH-MYCN mice

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. We established suitable spheroid culture condition that selectively isolates undifferentiated neuroblasts from superior mesenteric ganligon (SMG) of TH-MYCN mice. In the present study, in order to investigate the transcriptomic differences between embryonic day 13.5 (E13.5) WT derived primary spheres and E13.5 TH-MYCN derived passageable spheres, we carried out microarray gene expression analysis. We investigated critical molecular events in MYCN-transformed neuroblastoma cells in TH-MYCN mice.

2017-04-01 | GSE87783 | GEO

Retinoic acid-free spheroid culture condition is suitable for growth of TH-MYCN neuroblasts

Project description:It has been already reported that there are undifferentiated/proliferating neuroblasts in the postnatal sympathetic ganglia in TH-MYCN mice. Given the fact that neuroblastoma is derived from sympathoadrenal progenitors which are originated from neural crest stem cells, we attempted to use the well-established culture condition that has been utilized to maintain derivatives of neural crest stem cells. However, the medium contained retinoic acid (RA) which is known to induce neuroblastoma differentiation and is used in clinical treatment against high-risk patients. In the present study, the medium with RA (RA (+) medium) and without RA (RA (-) medium) were compared. Since undifferentiated neuroblasts are observable at one of the sympathetic ganglia, superior mesenteric ganglion (SMG), in 3-week-old TH-MYCN hemizygote (TH-MYCN+/-) mice with 129+Ter/SvJcl mice background, we dissected and dissociated the SMG to prepare single cells. These cells were cultured in either RA (+) or RA (-) media. Spheres formed in either RA (+) or RA (-) medium were subjected to microarray analysis.

2017-04-01 | GSE87781 | GEO

Array comparative genomic hybridization of tumor tissue developed in TH-MYCN (hemizygote) mice [Agilent-015028]

Project description:In order to investigate the chromosomal alterations (gains or losses) of tumor tissuees developed in TH-MYCN mice, a neuroblastoma model, we carried out array comparative genomic hybridization. We investigated whether chromosomal alterations occured in the tumor tissues developed in the abdomen of TH-MYCN hemizygote mice.

2017-04-01 | GSE89739 | GEO

The transcriptional co-repressor Runx1t1 is essential for N-Myc-driven neuroblastoma tumorigenesis [RNA-Seq 2]

Project description:Changes in epigenetic regulation are believed to be a major contributing factor to neuroblastoma development. Using a large-scale in vivo mutagenesis screen in Th-MYCN transgenic mice, we identified a single point mutation in the transcriptional corepressor Runx1t1, that can block N-Myc-driven neuroblastoma tumorigenesis. The loss of function mutation disrupts a highly conserved zinc finger domain (NHR4) within Runx1t1. Crossing an independent Runx1t1 knockout model with Th-MYCN mice, demonstrated that Runx1t1 haploinsufficiency is enough to prevent neuroblastoma development and reverse ganglia hyperplasia. Silencing RUNX1T1 in human neuroblastoma cells resulted in decreased colony formation in vitro, and significant inhibition of tumor growth in vivo. Our results show that RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex that regulates the epigenomic landscape and chromatin accessibility, to control neuron-specific pathway genes and maintain an undifferentiated state. Runx1t1 thus represents an entirely novel and highly promising target not previously described in neuroblastoma.

2024-04-01 | GSE230264 | GEO

The transcriptional co-repressor Runx1t1 is essential for N-Myc-driven neuroblastoma tumorigenesis [RNA-Seq 1]

2024-04-01 | GSE230263 | GEO

The transcriptional co-repressor Runx1t1 is essential for N-Myc-driven neuroblastoma tumorigenesis [ATAC-Seq]

2024-04-01 | GSE230262 | GEO

The transcriptional co-repressor Runx1t1 is essential for N-Myc-driven neuroblastoma tumorigenesis [ChIP-Seq]

2024-04-01 | GSE230261 | GEO

RNA-seq transcriptomic analysis of mouse sympathetic neuroblasts and adrenal chromaffin cells

Project description:Adrenal chromaffin cells and sympathetic neuron are derived from neural crest precursors and both cell types can give rise to childhood cancer, neuroblastoma. However only limited is known about the mechanism of their development. Better understanding of their transcriptomic profiles during development could gives an insight into the cell fates acquisition as well as the origin of neuroblastoma. Yellow fluorescent protein expressing sympathetic neuroblasts and adrenal chromaffin cells were isolated from E12.5 TH-IRES-Cre;ROSA26-EYFP mouse embryos by fluorescence-activated cell sorting. Transcriptomic profiles of sympathetic neuroblasts and adrenal chromaffin cells from embryonic age (E)12.5 TH-IRES-Cre;ROSA26-EYFP mice were generated by RNA sequencing, in four paired biological replicates.

2019-05-24 | E-MTAB-7086 | biostudies-arrayexpress

The genetics of splicing in neuroblastoma

Project description:Regulation of mRNA splicing is a critical and tightly regulated cellular function, underlying the majority of proteomic diversity in our genomes. While disruption of this process is common in disease, the basic genetic complexity of alternative splicing in vivo remains poorly understood. To delineate the splicing landscape in disease, we used an integrative genomics approach and combined both genome and exon level transcriptome data in two somatic tissues (cerebella and peripheral ganglia) from a transgenic mouse model of neuroblastoma, a tumor that arises from peripheral ganglia. These data identify splicing quantitative trait loci (sQTL) that modulate differential splicing across the genome. Among these, an sQTL at FUBP1 revealed a splicing event that modulated levels of the MYC oncoprotein in human neuroblastoma-derived cell lines and correlated with outcome in neuroblastoma. Through this unbiased sQTL analysis, we also define de novo splicing motifs that serve as sites for recurrent mutations in cancer and lead to functional changes in exon expression, enhancing our understanding of the cancer genome. Exon expression from Superior Cervical Ganglia and Cerebellum from 102 backcrossed mice (TH-MYCN, FVB/NJ and 129/SvJ) were correlated with 349 genotyping markers to identify putative sQTL The mice were the N1 generation of a backcross between TH-MYCN (FVB/NJ background) and wild-type 129/SvJ: TH-MYCN (FVB/NJ) + 129/SvJ -> F1 (TH-MYCN FVB/NJ,129/SVJ) F1 (TH-MYCN FVB/NJ,129/SVJ) + 129/SvJ -> N1

2015-04-03 | E-GEOD-55248 | biostudies-arrayexpress

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