Primordial germ cells identified as one potential cell of origin of MYC rhabdoid tumors
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PROVIDER: PRJNA779861 | ENA |
REPOSITORIES: ENA
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Project description:Primordial germ cells identified as one potential cell of origin of MYC rhabdoid tumors
| PRJNA780430 | ENA
Project description:Primordial germ cells identified as one potential cell of origin of MYC rhabdoid tumors
| PRJNA780462 | ENA
Project description:Primordial germ cells identified as one potential cell of origin of MYC rhabdoid tumors
| PRJNA780463 | ENA
Project description:Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we established and characterized different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identified distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validated that MYC RT originate from these progenitor cells. We uncovered an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impaired tumor growth in vitro and in vivo.
2022-01-28 | GSE188654 | GEO
Project description:Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we established and characterized different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identified distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validated that MYC RT originate from these progenitor cells. We uncovered an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impaired tumor growth in vitro and in vivo.
2022-01-28 | GSE188815 | GEO
Project description:Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we established and characterized different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identified distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validated that MYC RT originate from these progenitor cells. We uncovered an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impaired tumor growth in vitro and in vivo.
2022-01-28 | GSE188816 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-28 | GSE188817 | GEO
Project description:Primordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals. We have generated a point mutation in the Ror2 gene that we know disrupts primordial germ cell migration in the developing mouse embryo. We used microarray analysis to determine if this defect is mediated through genome-wide or pathway-specific transcriptional changes. We analyzed primordial germ cells (PGCs) from 4 wild-type (WT) and 4 Ror2Y324C/Y324C mutant embryos using Oct4-DPE-EGFP. PGCs were collected during their active migratory state at embryonic day 9.5 (somite range 20-25).
2014-08-08 | E-GEOD-60179 | biostudies-arrayexpress
Project description:Primordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals. We have generated a point mutation in the Ror2 gene that we know disrupts primordial germ cell migration in the developing mouse embryo. We used microarray analysis to determine if this defect is mediated through genome-wide or pathway-specific transcriptional changes.
2014-08-08 | GSE60179 | GEO
Project description:The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are âZygotomaâ. Bisulphite converted DNA from 77 samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip
2016-04-01 | E-GEOD-70783 | biostudies-arrayexpress