Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA304004 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation [zebrafish RNA-Seq]
| PRJNA304001 | ENA
Project description:A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation [zebrafish ChIP-seq]
| PRJNA304003 | ENA
Project description:A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation [ATAC-Seq]
| PRJNA303999 | ENA
Project description:A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation [human cell line RNA-seq]
| PRJNA304002 | ENA
Project description:The “cancerized field” concept posits that cells of a given tissue share a potentially oncogenic mutation or insult and are thus cancer-prone, yet only discreet clones within the field initiate tumor formation. In melanoma, tumors frequently (~50%) carry the oncogenic BRAFV600E mutation that is also nearly always present in benign nevi that rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors and is then specifically re-expressed in melanoma tumors. Here, we show by live imaging transgenic zebrafish crestin reporters that single melanocytes in a cancerized field with oncogenic BRAFV600E and p53 tumor suppressor loss undergo a change that recapitulates the neural crest progenitor (NCP) state, and patches of these cells initiate early melanoma. The crestin element is regulated by the NCP transcription factor sox10. Forced sox10 overexpression in melanocytes accelerated melanoma formation, consistent with reprogramming to the NCP state and activation of super-enhancers that lead to melanoma. Our work highlights the importance of the reemergence of the NCP state as a barrier to melanoma initiation.
2016-06-08 | GSE61825 | GEO
Project description:The “cancerized field” concept posits that cells of a given tissue share a potentially oncogenic mutation or insult and are thus cancer-prone, yet only discreet clones within the field initiate tumor formation. In melanoma, tumors frequently (~50%) carry the oncogenic BRAFV600E mutation that is also nearly always present in benign nevi that rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors and is then specifically re-expressed in melanoma tumors. Here, we show by live imaging transgenic zebrafish crestin reporters that single melanocytes in a cancerized field with oncogenic BRAFV600E and p53 tumor suppressor loss undergo a change that recapitulates the neural crest progenitor (NCP) state, and patches of these cells initiate early melanoma. The crestin element is regulated by the NCP transcription factor sox10. Forced sox10 overexpression in melanocytes accelerated melanoma formation, consistent with reprogramming to the NCP state and activation of super-enhancers that lead to melanoma. Our work highlights the importance of the reemergence of the NCP state as a barrier to melanoma initiation.
2016-06-08 | GSE61823 | GEO
Project description:The stress of nucleotide pool reduction regulates transcription in neural crest and melanoma cells. To better understand the molecular response caused by nucleotide stress, we designed a chemical suppressor screen for leflunomide, an inhibitor of dihydroorate dehydrogenase. We found that alterations in the progesterone receptor (Pgr) activity suppressed the neural crest effects of leflunomide. To clarify the mechanism of action, we found that the RNA helicase protein, Ddx21, binds to Pgr, and loss of function of Ddx21 conferred resistance to nucleotide stress in zebrafish embryos. At the molecular level, nucleotide stress reduces DDX21 chromatin occupancy and thus, target gene expression. Together our results show that DDX21 is a transcriptional sensor and mediator of the nucleotide stress response.
2020-02-06 | PXD014433 | Pride
Project description:Oncogenes are only transforming in certain cellular contexts, a phenomenon called oncogenic competence. Here, using a combination of a human pluripotent stem cell-derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E along with additional mutations depends upon the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are largely resistant to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes.
2021-04-15 | GSE172028 | GEO
Project description:Emergence of neural crest identity is a key early step in melanoma formation [ChIP-Seq]
| PRJNA262500 | ENA