Similar Datasets
Project description:Supratentorial ependymomas (ST-EPNs) are aggressive and treatment-resistant pediatric brain tumors that form along the human cortex, with suspected origin from radial glia cells. Although histologically similar, ST-EPNs are molecularly classified into six distinct subgroups, many of them remaining understudied. Here, we integrated molecular cell states and spatial architecture to resolve the cellular origins and aberrant differentiation trajectories of ST-EPNs at single-cell resolution. We show that, while all ST-EPNs display a unified origin from neuroepithelial cells, different subgroups harbor highly diverse cell states and differentiation potential associated with neural or ependymal differentiation. Spatial mapping uncovered a higher-order structural tumor organization driven by presence of the mesenchymal state, and refines classical histological features based on detailed molecular resolution. By benchmarking a morpho-molecular cell-state classification system in different disease models and human tumors, we identified four cellular subtypes defined by the architecture of neurite-like extensions that mediate either self-renewal or fast, saltatory invasive phenotypes reminiscent of neurons during neurodevelopment. Collectively, our study provides a comprehensive framework for the study of ST-EPN cellular states, and reveals biologically relevant tumor compartmentalization with potential clinical implication.
2025-12-09 | GSE300150 | GEO
Project description:Supratentorial ependymomas (ST-EPNs) are aggressive and treatment-resistant pediatric brain tumors that form along the human cortex, with suspected origin from radial glia cells. Although histologically similar, ST-EPNs are molecularly classified into six distinct subgroups, many of them remaining understudied. Here, we integrated molecular cell states and spatial architecture to resolve the cellular origins and aberrant differentiation trajectories of ST-EPNs at single-cell resolution. We show that, while all ST-EPNs display a unified origin from neuroepithelial cells, different subgroups harbor highly diverse cell states and differentiation potential associated with neural or ependymal differentiation. Spatial mapping uncovered a higher-order structural tumor organization driven by presence of the mesenchymal state, and refines classical histological features based on detailed molecular resolution. By benchmarking a morpho-molecular cell-state classification system in different disease models and human tumors, we identified four cellular subtypes defined by the architecture of neurite-like extensions that mediate either self-renewal or fast, saltatory invasive phenotypes reminiscent of neurons during neurodevelopment. Collectively, our study provides a comprehensive framework for the study of ST-EPN cellular states, and reveals biologically relevant tumor compartmentalization with potential clinical implication.
2025-12-09 | GSE300146 | GEO
Project description:Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas
| PRJNA1081786 | ENA
Project description:Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas [Spatial Transcriptomics]
| PRJNA1279151 | ENA
Project description:Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas [scRNA-Seq]
| PRJNA1279122 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-31 | GSE248811 | GEO
Project description:Small-cell lung cancer (SCLC) is the most aggressive and lethal subtype of lung cancer, for which, better understandings of its biology are urgently needed. Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment (TME) and investigate their roles in tumorigenic processes. Here, we performed high-precision single-cell transcriptomic analysis of ~5000 individual cells from primary tumors (PTs) and matched normal adjacent tissues (NATs) from 11 SCLC patients, including one patient with both PT and relapsed tumor (RT). The comparison revealed an immunosuppressive landscape of human SCLC. Malignant cells in SCLC tumors exhibited diverse states mainly related to the cell cycle, immune, and hypoxic properties. Our data also revealed the intratumor heterogeneity (ITH) of key transcription factors (TFs) in SCLC and related gene expression patterns and functions. The non-neuroendocrine (non-NE) tumors were correlated with increased inflammatory gene signatures and immune cell infiltrates in SCLC, which contributed to better responses to immune checkpoint inhibitors. These findings indicate a significant heterogeneity of human SCLC, and intensive crosstalk between cancer cells and the TME at single-cell resolution, and thus, set the stage for a better understanding of the biology of SCLC as well as for developing new therapeutics for SCLC.
| S-EPMC9532437 | biostudies-literature
Project description:BackgroundEmerging evidence has underscored infiltrating immune cells in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Owing to screening programs, the prevalence of early-stage NSCLC is growing, but its high recurrence risk and poor survival impose an increasing demand for further understanding the TME.MethodsTissue and plasma samples from 33 resectable stage IA NSCLC patients were collected from the surgery and subject to histological and genomic analyses. The distribution of CD8+ T cells, tumor-associated macrophages (TAMs, M1 polarization and M2 polarization), and natural killer (NK) cells (CD56dim and CD56bright) was analyzed. The impact of clinical characteristics and immunotherapy-related biomarkers on immune cell infiltration were also investigated.ResultsUsing multiplex immunohistochemistry (mIHC), we found a significantly higher M1 polarization proportion of total TAMs in tumor parenchyma than in other tissues, while other immune cells remained stable. Patients under 50 showed higher infiltrating CD8+ T cell density and M1 ratio in tumor tissues. Tumors carrying RAS-MAPK mutations were associated with significantly increased infiltration of CD8+ T cells. We also identified significantly higher infiltration of CD8+ T cells and enrichment of CD56bright NK cells in high tumor mutation burden (TMB) and high programmed cell death ligand 1 (PD-L1) samples, respectively.ConclusionsOur study highlighted the heterogeneity and dynamics of infiltrating immune cells in stage IA NSCLC TME, featured by M1 TAM enrichment in tumor parenchyma. Age, driver mutation type, TMB, and PD-L1 level were found to associate with immune cell infiltration in the TME, shedding light on immunotherapy development.
| S-EPMC8977165 | biostudies-literature
Project description:The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.
| S-EPMC10333192 | biostudies-literature
Project description:No reliable classification is in clinical use for the therapeutic stratification of children with ependymoma, such that disease risk might be identified and patients treated to ensure a combination of maximal cure rates and minimal adverse therapeutic effects. This study has examined associations between clinicopathologic and cytogenetic variables and outcome in a trial cohort of children with ependymoma, with the aim of defining a practical scheme for stratifying this heterogeneous tumor. Intracranial ependymomas (n = 146) from children treated on the RT1 trial at St. Jude Children's Research Hospital were evaluated for the status of multiple pathological features. Interphase FISH (iFISH) defined the status of loci on chromosomes 1q (EXO1), 6q (LATS1) and 9, including 9p21 (CDKN2A). Data relating to these clinicopathological and cytogenetic variables were compared with survival data in order to model disease risk groups. Extent of surgical resection was a significant determinant of outcome in both supratentorial and infratentorial compartments. Tumor cell density and mitotic count were associated with outcome among children with posterior fossa ependymomas (n = 119). Among pathologic features, only brain invasion was associated with outcome in children with supratentorial ependymomas (n = 27). For posterior fossa tumors, gain of 1q was independently associated with outcome and in combination with clinicopathological variables defined both a two-tier and three-tier system of disease risk. Among children developing posterior fossa ependymomas treated with maximal surgical resection and conformal radiotherapy, key clinicopathological variables and chromosome 1q status can be used to define tiers of disease risk. In contrast, risk factors for pediatric supratentorial tumors are limited to sub-total resection and brain invasion.
| S-EPMC3554251 | biostudies-literature