Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [scWGS]

ABSTRACT: Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173279 | GEO | 2022/02/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [scRNA-seq]

Project description:Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.

2022-02-16 | GSE173278 | GEO

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity [multi-generation scRNA-seq]

2022-02-16 | GSE193884 | GEO

Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity

| EGAS00001005227 | EGA

Patient and xenograft-derived organoids recapitulate pediatric brain tumors features and patient treatments [scRNA-Seq]

Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.

2023-12-01 | GSE247380 | GEO

Patient and xenograft-derived organoids recapitulate pediatric brain tumors features and patient treatments [array]

2023-12-01 | GSE247231 | GEO

Patient-derived Organoids Predicts the Clinical Efficiency of Colorectal Liver Metastasis

Project description:Accumulating evidence indicates that patient- derived organoids (PDOs) can predict drug responses in the clinic. Metastasis is the main cause of death in colorectal cancer patients, and the treatment of patients with liver metastasis remains poor. Tumor heterogeneity is the cause of treatment failure. In this study, we aim the investigate the consistency of drug sensitivity for the matched primary and metastatic tumor in patients with liver metastasis.

| 2400343 | ecrin-mdr-crc

Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (gene expression)

Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. Gene expression profiling experiments were conducted for 58 human glioblastoma samples using Affymetrix Human Gene 1.0 ST arrays according to manufacturer's protocol.

2013-01-18 | E-GEOD-42669 | biostudies-arrayexpress

Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (CGH)

Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. aCGH experiments were performed for a human glioblastoma tissue (sample ID: PC-NS08-559) and the matching xenograft tumor tissue using the Agilent Human Whole Genome CGH 244K microarray according to manufacturer's protocol (2-color).

2013-01-18 | E-GEOD-42577 | biostudies-arrayexpress

Bladder cancer organoids as a functional system to model different disease stages and therapy response

Project description:Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancers. In our study, we established PDO cultures from different BLCa stages and grades. PDOs preserve the histological and molecular heterogeneity of the parental tumors (PTs), including their multiclonal genetic landscapes, and consistently share key genetic alterations, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline was implemented using PDOs, testing both standard-of-care and FDA-approved compounds for other tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis was used to determine enrichment thresholds for candidate markers of therapy response and resistance. Finally, by assessing the clinical history of longitudinally sampled cases we were able to assess the disease clonal evolution matched with drug response.

2023-02-01 | GSE217956 | GEO

Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (CGH)

2013-01-18 | GSE42577 | GEO