Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

ABSTRACT: Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

PROVIDER: PRJNA777110 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR16693906_1.fastq.gz	Fastqsanger.gz
	SRR16693906_2.fastq.gz	Fastqsanger.gz
	SRR16693907_1.fastq.gz	Fastqsanger.gz
	SRR16693907_2.fastq.gz	Fastqsanger.gz
	SRR16693908_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 114

Similar Datasets

Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

Project description:Method: In this study we use single cell RNA sequencing (scRNA-seq) to distinguish HB tumor cells from non-tumor cells and to identify distinct tumor cell types that account for the heterogeneity of HB. We also use a novel method to grow HB tumor cells as patient-specific spheroids (PDS) and show how this can be used to predict treatment response and identify novel therapeutic targets. Results: This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Conclusions: These results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

2022-03-01 | GSE186975 | GEO

Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids.

Project description:Pediatric hepatoblastoma is the most common primary liver cancer in infants and children. Studies of hepatoblastoma that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, hepatoblastoma tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we use single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens, and identify five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease. Notably, patient-derived hepatoblastoma spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. In this work, we define hepatoblastoma tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

| S-EPMC9411569 | biostudies-literature

EZH2 is a key component of Hepatoblastoma tumor cell growth

Project description:To understand molecular mechanisms driving HB pathogenesis, we hypothesize that pathologic activation of Enhancer of Zeste Homolog 2 contributes to hepatoblastoma propagation. Here we demonstrate that EZH2 promotes proliferation in HB cell lines through interaction with β-catenin, the most frequently mutated gene in HB. We demonstrate that canonical and noncanonical EZH2 signaling occur in HB tumor cells, likely driven by aberrant EZH2 expression. We use comparison groups of liver cancer, hepatocytes, and dermal fibroblasts to establish the hepatoblastoma identity of our patient-derived cell lines.

2023-11-15 | GSE235202 | GEO

Genome-wide mapping of oncogenic pathways and genetic modifiers of chemotherapy using a high-risk hepatoblastoma genetic model

Project description:Lack of relevant disease animal models and cell lines hampers our understanding of hepatoblastoma and identification of therapeutic targets. We report a liver-specific MYC-driven hepatoblastoma murine model that faithfully recapitulates the pathological features of mixed fetal and embryonic hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of human disease. Single-cell RNA-sequencing (scRNA-seq) and spatiotranscriptomics identify a subpopulation of hepatoblastoma cells with high levels of adult hemoglobin genes. After deriving a cell line from the mouse model, we mapped the cancer dependency genes using CRISPR-Cas9 and identified druggable targets shared with human hepatoblastoma (i.e., CDK7, CDK9, PRMT1, PRMT5). Our screen also discovered oncogenes and tumor suppressive genes in hepatoblastoma that engage multiple cancer signaling pathways. Chemotherapy is the mainstay of human hepatoblastoma. Genetic map of doxorubicin response by CRISPR-Cas9 identified modifiers whose loss-of-function synergizes (PRKDC) and antagonizes (Polycomb repressive complex 2) the effect of chemotherapy. Combination of PRKDC inhibitor and chemotherapy greatly enhances therapeutic efficacy. Our studies have provided useful disease models and potential therapeutic targets of hepatoblastoma.

2023-06-22 | GSE193124 | GEO

Hepatic transcriptome of pediatric hepatoblastoma.

Project description:The mechanisms underlying hepatoblastoma are not well defined. To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing. Hepatoblasoma was histologically confirmed. Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children.

2018-07-01 | GSE81928 | GEO

EZH2 is a key component of Hepatoblastoma tumor cell growth

Project description:EZH2 is a key component of Hepatoblastoma tumor cell growth

| PRJNA985457 | ENA

Modeling Hepatoblastoma

Project description:Modeling Hepatoblastoma

| PRJNA749045 | ENA

Mixed cell-type spheroids endorse the generation and maintenance of heme-TAMs in an experimental tumor microenvironment

Project description:To more accurately mimic the tumor microenvironment, we established a three-dimensional culture of MC38 cancer cells mixed with heme-treated BMDMs in microwell plates. This resulted in tumor spheroids with uniformly interspersed macrophages. We profiled the transcriptome of macrophages within these spheroids using scRNA-seq 24 hours after spheroid formation. To test the robustness of the heme effects in this model, we conducted a multiplexed experiment evaluating heme alone and in combination with the classical M1-polarization stimuli INFγ and LPS.

2024-01-03 | GSE236576 | GEO

Tracking transcriptional changes in a species-specific manner during experimental hepatoblastoma progression in vivo

Project description:Hepatoblastoma is a primitive liver cancer occurring mainly in infants with defined molecular alterations driving its progression, which is difficult to model in vivo. Here we present a new animal model for hepatoblastoma on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of hepatoblastoma in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of hepatoblastoma cells on the CAM, with significant deregulation of more than 6000 genes including more than half of all HOX genes. Bioinformatic analysis could clearly distinguish between tumor cell-expressed genes and chick host genes, thereby shedding new light on the complex interactions taking place during experimental hepatoblastoma progression. Importantly, human tumor suppressive ribosomal genes were downregulated after implantation, whereas mitochondrial genes encoding for anti-apoptotic peptides were strongly induced in vivo. Meprin-1α expression was increased during evolution of CAM tumors and confirmed by immunohistochemistry. Cisplatin, a commonly used chemotherapeutic agent for hepatoblastoma, showed significant anti-tumoral effects in this model. Our results broaden the understanding of the molecular adaptation process of human cancer cells to the microenvironment and might help to elaborate novel therapeutic concepts for the treatment of this pediatric liver tumor.

2018-04-17 | GSE101413 | GEO

Transcription profiling of human ovarian cancer cell lines grown as multicellular spheroids and treated with three chemotherapy drugs

Project description:Gene expression profiling of ovarian cancer spheroids upon treatment with three chemotherapy drugs

2008-05-06 | E-MEXP-1319 | biostudies-arrayexpress