Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription profiling of mouse early and aduly developmental stages

ABSTRACT: DNA repair genes have been shown to be expressed in the early stages of mammalian development probably to reduce possible replication errors and genotoixc damages. Several birth defects and some cancers are due to inappropriate or defective DNA repair machinery indicating that a right activity of DNA repair genes in the early stages of fetal development are essential for an appropriate DNA function. Neuroblastoma (NB), an embryonal tumor deriving from neural crest cells (NCCs) is diagnosed in about 30% of patients within the first year of life. Moreover, several reports show that NB can be detected in foetus and in neonatal period. To assess gene expression profiling of DNA repair genes during early stage of development, we performed a genome-wide analysis of Neural Crest cells (NCCs) generating a gene expression database that can help to better understand the gene(s) involved in both genetic and cancer diseases. We found 11 genes involved in DNA repair activity during mouse embryo development overexpressed in early stages. Six out 11 were never been described in mouse embryology. Experiment Overall Design: Mouse embryos were collected at successive stages of early and adult development stages for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of NCCs by Laser Capture Microdissection (LCM) from embryos and adult in order to analyze DNA repair genes during mouse development. To that end, we collected cells at three time-points: at embryonal stage of 8.5 dpc: E8.5 (neural tube closure); at embryonal stage of 13.5dpc: E13.5 (dorsal root ganglion); at adult stage of 3 months postnatal: P90 (adrenal medulla).

ORGANISM(S): Mus musculus

SUBMITTER: Domenico Albino

PROVIDER: E-GEOD-11356 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression data from early and adult stages of mouse development

Project description:DNA repair genes have been shown to be expressed in the early stages of mammalian development probably to reduce possible replication errors and genotoixc damages. Several birth defects and some cancers are due to inappropriate or defective DNA repair machinery indicating that a right activity of DNA repair genes in the early stages of fetal development are essential for an appropriate DNA function. Neuroblastoma (NB), an embryonal tumor deriving from neural crest cells (NCCs) is diagnosed in about 30% of patients within the first year of life. Moreover, several reports show that NB can be detected in foetus and in neonatal period. To assess gene expression profiling of DNA repair genes during early stage of development, we performed a genome-wide analysis of Neural Crest cells (NCCs) generating a gene expression database that can help to better understand the gene(s) involved in both genetic and cancer diseases. We found 11 genes involved in DNA repair activity during mouse embryo development overexpressed in early stages. Six out 11 were never been described in mouse embryology. Keywords: time course

2008-05-06 | GSE11356 | GEO

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

Project description:Neuroblastoma (NB) arises from neural crest cells (NCCs) secondary to a block in differentiation. Retinoic acid (RA) differentiation therapy has limited therapeutic efficacy, and the mechanisms preventing terminal differentiation remain elusive. We found that the chromatin modifier CHAF1A restricts neuronal differentiation and promotes NB oncogenesis. CHAF1A blocks NC differentiation into mature neurons in both human NCCs and zebrafish models. CHAF1A gain-of-function promotes cell malignancy, blocks RA-induced differentiation, and is sufficient to induce NB tumor formation. Mechanistically, CHAF1A blocks NB differentiation by repressing gene expression programs promoting neuronal development and differentiation, and rewiring polyamine metabolism. Targeting polyamine synthesis restores NB sensitivity to RA therapy. Our results demonstrate that CHAF1A critically contributes to NB oncogenesis by blocking neuronal differentiation and reprogramming cell metabolism.

2021-07-20 | GSE144311 | GEO

CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity

Project description:Pleiotropic genetic factors (e.g., DNA polymorphisms) may be involved in the initiation of neuroblastoma (NB) and coronary artery disease (CAD) given their common origin from defects in neural crest development. To discover novel NB susceptibility genes, we conducted a three-stage survey including a meta-analysis of NB and CAD genome-wide association data, prioritization of NB causal variants, and validation in an independent case-controls cohort. The lead SNP, rs13337397 at the 16q23.1 locus, associated with both diseases in the meta-analysis and with NB in the validation study. All the SNPs in linkage disequilibrium with rs13337397 were annotated using the H3K27ac epigenetic marker of neural crest cells (NCC) and NB cell lines. Indeed, we identified the functional SNP rs13337017, mapping within an enhancer of NCCs and NB cell lines and showing long-range interactions with CFDP1 by Hi-C analysis. Luciferase assays indicated that the risk allele of rs13337017 increased CFDP1 expression in NB cell lines. Of note, CFDP1 high expression associated with unfavorable prognostic markers in an analysis including 498 NB transcriptomes. Moreover, depletion of CFDP1 markedly decreased viability and migration and increased apoptotic rates in NB cell lines. Finally, transcriptome and qPCR analyses revealed that the depletion of CFDP1 may affect noradrenergic neuron differentiation by downregulating master regulators of sympathetic noradrenergic identity, including PHOX2B, HAND2 and GATA3. Our data strongly suggest that CFDP1 acts as oncogene in NB. Additionally, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.

2022-10-30 | GSE216674 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [ATAC-seq]

Project description:Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

2024-03-22 | GSE219151 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [RNA-seq]

2024-03-22 | GSE219149 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [Parse scRNA-seq]

2024-03-22 | GSE262111 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [10x scRNA-seq]

2024-03-22 | GSE221853 | GEO

An atlas of neural crest lineages along the posterior developing zebrafish at single-cell resolution

Project description:Neural crest cells (NCCs) are vertebrate stem cells that give rise to various cell types throughout the developing body in early life. Here, we utilized single-cell transcriptomic analyses to delineate NCC-derivatives along the posterior developing vertebrate, zebrafish, during the late embryonic to early larval stage, a period when NCCs are actively differentiating into distinct cellular lineages. We identified several major NCC/NCC-derived cell-types including mesenchyme, neural crest, neural, neuronal, glial, and pigment, from which we resolved over three dozen cellular subtypes. We dissected gene expression signatures of pigment progenitors delineating into chromatophore lineages, mesenchyme subtypes, and enteric NCCs transforming into enteric neurons. Global analysis of NCC derivatives revealed they were demarcated by combinatorial hox gene codes, with distinct profiles within neuronal cells. From these analyses, we present a comprehensive cell-type atlas that can be utilized as a valuable resource for further mechanistic and evolutionary investigations of NCC differentiation.

2021-02-16 | GSE152906 | GEO

MYCN induces neuroblastoma in primary neural crest cells

Project description:Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS) that causes 15% of pediatric cancer deaths. High-risk neuroblastoma is characterized by N-Myc amplification and segmental chromosomal gains and losses. Due to limited disease models, the etiology of neuroblastoma is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying neuroblastoma based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived neuroblastoma tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified neuroblastoma including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human neuroblastoma and establishes a new system with potential to study early stages of neuroblastoma oncogenesis, to functionally assess neuroblastoma oncogenic drivers, and to characterize neuroblastoma metastasis.

2017-09-25 | GSE94914 | GEO

The BAF chromatin remodeling complex regulates gene expression programs essential for mammalian neural crest development

Project description:Neural crest cells (NCCs) are a multipotent cell population that contributes to the development of many tissues including craniofacial, pharyngeal arch arteries, and cardiac outflow tract (OFT). The BAF complex plays an important role in the development of a wide range of tissues by modulating gene expression programs at the chromatin level. However, its role in neural crest development has remained unclear. To determine the role BAF complex, we deleted BAF155 and BAF170, the core subunits required for the assembly, stability, and functions of the BAF complex in NCCs. Mouse embryos lacking BAF155/170 in NCCs displayed early lethality due to a wide range of developmental defects including craniofacial defects, pharyngeal arch artery defects, and OFT defects. We observed reduced proliferation, increased cell death, and impaired migration of cardiac NCCs to the OFT in BAF155/170 mutants. RNAseq analysis on sorted NCCs revealed that the BAF complex regulates the expression of numerous genes essential for neural crest development. We observed downregulation of Hippo and Notch signaling pathways, both essential for the migration, proliferation, and differentiation of the NCCs. The BAF complex interacts with transcription factors to modulate the transcriptional program. Therefore, we performed transcription factor enrichment analysis on the RNAseq data set and identified several transcription factors including Hey1, Hey2, and Hes5 that may directly or indirectly interact with the BAF complex in NCCs. We also found that Brg1 interact with Tead transcription factors and the interaction was impaired in BAF155/170 knockdown cells. Together, our results demonstrate an important role of the BAF complex in modulating the gene regulatory network essential for neural crest development.

2021-03-05 | GSE153121 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data