A3f5f150-7982-40a6-a5e5-5325c520be56 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001015012 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.
| EGAD00001015413 | EGA
Project description:Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.
| EGAD00001015414 | EGA
Project description:Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.
| EGAS00001007650 | EGA
Project description:Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting effects. However BPA replacement chemicals are structurally similar, and little data exist describing their effects on the human body and environment. We established non-malignant human mammary organoid cultures to investigate the effects of BPA replacement chemicals on organoid morphology and protein abundance. At low-nanomolar doses, replacement chemicals, in particular BPS, induced branching and disrupted the organized mammary organoid architecture. BPS exposure likely alters mammary cell-type proportions and induces branching of predominately myoepithelial cells. Treatment with different replacement chemicals resulted in distinct proteomic changes. BPS exposure induced Cdc42-interacting protein 4 (CIP4), a protein known to support invadopodia formation and mesenchymal phenotypes. Our study provides evidence that replacement bisphenols have pro-tumorigenic effects on mammary morphology and the proteome, highlighting the necessity of comprehensive studies to evaluate the potential harm of replacement chemicals.
2021-06-11 | MSV000087617 | MassIVE
Project description:Microglia and border-associated macrophages (BAMs) are critical for brain health and their dysfunction is closely linked to disease. Replacing brain macrophages holds significant therapeutic promise, but remains challenging. Here, we demonstrate that monocytes can efficienty replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably to their embryonic counterparts and showed similar longevity. However, monocytes were unable to replicate the unique identity of embryonically-derived BAMs and microglia. Using humanized models, we found that human monocytes exhibited similar behavior, enabling us to identify putative Mo-Microglia in Alzheimer’s disease patients. In mice and humans, the ontogeny of monocytes shaped their identity as brain macrophages. Importantly, mouse fetal liver monocytes exhibited a distinct epigenetic landscape and could develop a bonafide microglial identity. Our results illuminate brain macrophage development and highlight the potential of monocytes as an abundant progenitor source for brain macrophage replacement therapies.
2025-04-22 | GSE292830 | GEO
Project description:Deciphering spatial domains from spatial multi-omics with SpatialGlue
| PRJNA1098416 | ENA
Project description:Following DPST crosslinking of human neuroblastoma cells, nuclear-cytoplasmic fractionation was performed using hypotonic lysis to obtain cytoplasmic and nuclear protein compartments. Through systematic analysis of crosslinking mass spectrometry data, we elucidated how subcellular compartmentalized microenvironments regulate spatial distribution of protein conformations and topological architecture of interaction networks. This study reveals the heterogeneous principles governing dynamic protein assembly between nuclear and cytoplasmic compartments in neuroblastoma cells.
2025-04-14 | PXD062913 |
Project description:Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis.
2021-06-20 | GSE178498 | GEO
Project description:MYCN-amplification is a strong predictor of poor prognosis in neuroblastoma, an embryonal malignancy that accounts for 15% of pediatric cancer deaths. Here, we found that MYCN-amplified neuroblastoma tumors have increased 5-hydroxymethylcytosine (5-hmC) deposition on Polycomb Repressive Complex 2 (PRC2) target genes. 5-hmC and H3K27me3, a catalytic product of PRC2, directly co-localize at the nucleosomal level in MYCN-amplified neuroblastoma. Genes with co-localization of 5-hmC/H3K27me3 are involved in development related pathways and are transcriptionally repressed in MYCN-amplified neuroblastoma. Chemical and genetic inhibition of 5-hmC deposition results in a loss of H3K27me3 deposition on protein-coding genes. Furthermore, 5-hmC deposition predisposes H3K27me3 marked genes to transcriptional activation upon PRC2 inhibition with tazemetostat. Low expression of genes marked by 5-hmC/H3K27me3 is associated with poor clinical outcome. Our results suggest that 5-hmC/H3K27me3 co-operate to repress mediators of development highlighting a novel link between DNA modifications and chromatin modifications with potential therapeutic implications in MYCN-amplified neuroblastoma.
2026-05-12 | GSE294307 | GEO
Project description:MYCN-amplification is a strong predictor of poor prognosis in neuroblastoma, an embryonal malignancy that accounts for 15% of pediatric cancer deaths. Here, we found that MYCN-amplified neuroblastoma tumors have increased 5-hydroxymethylcytosine (5-hmC) deposition on Polycomb Repressive Complex 2 (PRC2) target genes. 5-hmC and H3K27me3, a catalytic product of PRC2, directly co-localize at the nucleosomal level in MYCN-amplified neuroblastoma. Genes with co-localization of 5-hmC/H3K27me3 are involved in development related pathways and are transcriptionally repressed in MYCN-amplified neuroblastoma. Chemical and genetic inhibition of 5-hmC deposition results in a loss of H3K27me3 deposition on protein-coding genes. Furthermore, 5-hmC deposition predisposes H3K27me3 marked genes to transcriptional activation upon PRC2 inhibition with tazemetostat. Low expression of genes marked by 5-hmC/H3K27me3 is associated with poor clinical outcome. Our results suggest that 5-hmC/H3K27me3 co-operate to repress mediators of development highlighting a novel link between DNA modifications and chromatin modifications with potential therapeutic implications in MYCN-amplified neuroblastoma.
2026-05-12 | GSE294308 | GEO