Browse Projects
Number of Projects: 7
Size: 851.33 MB

Includes Bulk RNA-Seq

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26 Downloadable Samples

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Cell

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10Xv3

DiagnosisPilocytic astrocytoma (16), Ganglioglioma (5), Low grade glioma (3), Ganglioglioma/ATRT (1), Ependymoma (1)
AbstractPediatric brain tumors are now the most common cause of mortality from disease in childhood. Molecular characteristics of pediatric high- and low-grade gliomas (PHGG and PLGG), the most common tumor category overall, are crucial to treatment and outcomes, but the impact of these characteristics and of the variety of cell populations in these tumors is poorly understood. We performed single-cell RNA-sequencing on viably banked single cell samples of high- and low- grade glial tumors from children treated at Children’s Hospital Colorado. These samples are part of ongoing single-cell pediatric brain tumor banking that our group initiated a decade ago. The maturity of this resource, collected over a decade, provides us with the opportunity to perform well-powered outcome association studies. Samples are collected during routine surgery and immediately disaggregated to isolate single cells. These are then viably frozen in DMSO and banked for later use. We have tumors that cover the variety of subtypes in each of these diseases, as well as comprehensive clinical information on these cases, which will allow us to correlate molecular subtypes and research findings with these clinical measures. Here, we perform single-cell RNA-sequencing on 26 samples from patients with PLGG. In PLGG, we will leverage scRNA-Seq analysis to identify lineage specific development and subpopulations within these tumors. We will then evaluate single-cell RNA-sequencing signatures and clinical outcomes of LGG with BRAF WT, KIAA1549:BRAF fusion and BRAFV600E to identify unique drivers of aggressiveness of BRAFV600E tumors. These studies will significantly advance our understanding of disease biology and provide the detailed molecular and functional insights needed to identify new therapeutic targets for these biologically and clinically heterogeneous tumors.
Additional Sample Metadata Fieldssubmitter, BRAF_status, scpca_project_id, participant_id, submitter_id, spinal_leptomeningeal_mets
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23 Downloadable Samples

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Cell, Nucleus

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10Xv3.1, 10Xv3, 10Xv2

DiagnosisNeuroblastoma (23)
AbstractPediatric solid tumors are rare compared to common adult malignancies and they are also remarkably diverse. For example, rhabdomyosarcomas have features of skeletal muscle, osteosarcomas have features of bone and neuroblastomas have features of cells in the sympathoadrenal lineage. The diversity and rarity of pediatric solid tumors makes it difficult to accelerate biomedical research that can improve patient outcomes. For example, even with the large number of patients treated at St. Jude, it can be difficult to obtain fresh pediatric solid tumor tissue that is suitable for single cell sequencing. To overcome this barrier in the field, we have collaborated with Aviv Regev at the Broad Institute to compare single-cell RNA-sequencing to single-nuclei RNA-sequencing for pediatric solid tumors. Our data show that we can capture the transcriptional heterogeneity of the tumors and the complexity of the tumor microenvironment using single-nuclei RNA-sequencing of patient tumors from the St. Jude biorepository. In addition, over the past 9 years, we have generated 166 orthotopic patient derived xenografts (O-PDXs) representing 21 different pediatric solid tumor types. The O-PDXs and corresponding patient tumors have undergone some of the most comprehensive characterization of any pediatric cancer model including detailed analysis of the clonal heterogeneity (Stewart et al. Nature, 2018). We performed single-cell or single-nuclei RNA-sequencing of 23 tissue samples obtained from Neuroblastoma patients as part of a larger effort to perform single-cell/single-nuclei RNA-sequencing on a large cohort of patient tumors and O-PDXs. This research proposal will fill a fundamental gap in our knowledge of the transcriptome heterogeneity across pediatric solid tumor clones and of the normal cells found in the tumor microenvironment.
Additional Sample Metadata Fieldsprimary_site, scpca_project_id, IGSS_stage, treatment_status, MYCN_status, submitter, COG_risk, participant_id, submitter_id
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45 Downloadable Samples

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Cell, Nucleus

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10Xv3, 10Xv2

DiagnosisRhabdomyosarcoma (45)
AbstractPediatric solid tumors are rare compared to common adult malignancies and they are also remarkably diverse. For example, rhabdomyosarcomas have features of skeletal muscle, osteosarcomas have features of bone and neuroblastomas have features of cells in the sympathoadrenal lineage. The diversity and rarity of pediatric solid tumors makes it difficult to accelerate biomedical research that can improve patient outcomes. For example, even with the large number of patients treated at St. Jude, it can be difficult to obtain fresh pediatric solid tumor tissue that is suitable for single cell sequencing. To overcome this barrier in the field, we have collaborated with Aviv Regev at the Broad Institute to compare single-cell RNA-sequencing to single-nuclei RNA-sequencing for pediatric solid tumors. Our data show that we can capture the transcriptional heterogeneity of the tumors and the complexity of the tumor microenvironment using single-nuclei RNA-sequencing of patient tumors from the St. Jude biorepository. In addition, over the past 9 years, we have generated 166 orthotopic patient derived xenografts (O-PDXs) representing 21 different pediatric solid tumor types. The O-PDXs and corresponding patient tumors have undergone some of the most comprehensive characterization of any pediatric cancer model including detailed analysis of the clonal heterogeneity (Stewart et al. Nature, 2018). We performed single-cell or single-nuclei RNA-sequencing of 45 tissue samples from both Rhabdomyosarcoma patient tumors and matched O-PDXs as part of a larger effort to perform single-cell/single-nuclei RNA-sequencing on a large cohort of patient tumors and O-PDXs. This research proposal will fill a fundamental gap in our knowledge of the transcriptome heterogeneity across pediatric solid tumor clones and of the normal cells found in the tumor microenvironment.
Additional Sample Metadata Fieldsprimary_site, scpca_project_id, sample_type, stage, fusion_status, treatment_status, primary_or_metastasis, submitter, group, participant_id, risk_stratum, submitter_id
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38 Downloadable Samples

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Nucleus

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10Xv3.1

DiagnosisWilms tumor (38)
AbstractWilms tumor (WT) is the most common pediatric kidney cancer. WT is characterized by a significant degree of intratumor subclonal histologic and genetic heterogeneity. Histology is the greatest predictor of outcome, and patients with unfavorable histology (diffuse anaplasia) account for 5% of cases, but 50% of deaths from this disease. A critical barrier to understanding therapeutic resistance in WT is that resistant cells, particularly the anaplastic population in unfavorable histology WT, may represent a minor subclone in the tumor. Therefore, prior analyses based on bulk genome and RNA-sequencing may have failed to identify new anaplasia-specific therapeutic targets because of dilution by non-anaplastic cells in the tumor. Our preliminary single-cell RNA-sequencing experiments have revealed substantial transcriptomic heterogeneity in anaplastic and favorable histology WT patient derived xenografts. However, it has been challenging to assign specific cluster(s) to the anaplastic populations unambiguously. The purpose of this project is to resolve the transcriptome of the blastemal, epithelial, and stromal cellular populations in Wilms tumor and to unambiguously identify the expression signature of anaplastic clones in anaplastic histology WT. We aim to achieve this goal by analyzing 23 favorable histology WT and 22 anaplastic histology WT with single-nuclei RNA sequencing. This study will help establish an anaplasia-specific expression signature in unfavorable histology WT. Furthermore, our approach will also identify how tumor-stromal interactions, which play a key role in therapeutic resistance, may differ between anaplastic and favorable histology components within unfavorable histology WT. The long-term intellectual impact of this study is that the expression signature established by our work is likely to advance the understanding of therapeutic resistance in this treatment refractory tumor subtype.
Additional Sample Metadata Fieldsmetastasis, scpca_project_id, relapse_status, submitter, vital_status, participant_id, submitter_id
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30 Downloadable Samples

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Cell

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10Xv2_5prime

DiagnosisAcute myeloid leukemia (26), T-myeloid mixed phenotype acute leukemia (2), Non-cancerous (2)
AbstractBulk genomic studies of tens of thousands of acute myeloid leukemia (AML) cells mixed together have cataloged the changes in gene expression and mutations present in at least 10-20% of cells. The discoveries from these studies have implicated a number of new genes in AML formation, progression, and persistence, resulting in further subclassification of the disease. Still, these discoveries have thus far not been translated into improved outcomes for patients. This is in large part due to the heterogeneity of cell types and genomic changes within the cells that are present within a sample. The development of technologies to sequence genomes, quantify transcriptomes and identify surface proteomes of single cells has afforded a new opportunity to dissect and better understand the biology of these distinct cell types. In this study, we perform single-cell RNA sequencing and CITE-seq of 30 AML samples. Using cell types identified from single-cell RNA-sequencing with CITE-seq, cells are sorted based on expression of surface markers unique to phenotypic AML subpopulations. This is followed by whole genome amplification using our newly invented primary template-directed amplification (PTA) to perform accurate variant calling of the 1.2 Mb of the genome most commonly mutated in AML samples, as well as low-pass whole genome sequencing for single cell copy number variation profiling. Data from these studies will be used to identify distinct cell types present in AML samples including cells that appear to be of non-myeloid origin. This data will enable the exploration of transcriptomic changes present in distinct AML subpopulations. We anticipate the new insights afforded by this high-resolution resource will provide a deeper understanding of AML that could uncover new treatment approaches for this deadly pediatric cancer.
Additional Sample Metadata Fieldsscpca_project_id, submitter_id, submitter, participant_id
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4 Downloadable Samples

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Nucleus

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10Xv3.1

35 more samples will be made available soon
DiagnosisEpendymoma (1), Dysplastic gangliocytoma (1), Dysembryoplastic neuroepithelial tumor (1), Glioblastoma (1)
AbstractSingle cell gene expression profiling of pediatric central nervous system (CNS) tumors holds great potential to further our understanding of carcinogenesis, augment prognostic indicators, and identify rational therapeutic targets. Whereas the genomic characteristics of these tumors are fairly well-defined in aggregate, the extent to which cellular heterogeneity is associated with carcinogenesis and clinical outcomes is largely unknown. Here we profile single nuclei gene expression in 36 brain tumor specimens from individuals with a diagnosis of ependymoma, glioma, or embryonal CNS tumor with substantial follow up time, as well as non-tumor brain tissue from three pediatric controls. We used the 10X Genomics Single Cell platform to obtain single nuclei for RNA sequencing in conjunction with bulk RNA sequencing. In conjunction with this study, we obtained 5-methyl- and 5-hydroxymethylation profiles on these samples to investigate functional aspects of gene regulation by cytosine modification. The data and results from this study are expected to reveal an abundance of information about pediatric CNS tumors with value for the broader scientific community.
Additional Sample Metadata Fieldsscpca_project_id, WHO_grade, participant_id, location_class, submitter_id, Developed_recurrence, submitter, Years_to_recurrence
Size: 653.86 MB

Includes Bulk RNA-Seq

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23 Downloadable Samples

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Cell

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10Xv3

DiagnosisAnaplastic glioma (1), Glioblastoma (16), High grade glioma (2), Diffuse midline glioma (1), Non-cancerous (1), Pleomorphic xanthoastrocytoma (1), Anaplastic astrocytoma (1)
AbstractPediatric brain tumors are now the most common cause of mortality from disease in childhood. Molecular characteristics of pediatric high- and low-grade gliomas (PHGG and PLGG), the most common tumor category overall, are crucial to treatment and outcomes, but the impact of these characteristics and of the variety of cell populations in these tumors is poorly understood. We performed single-cell RNA-sequencing on viably banked single cell samples of high- and low- grade glial tumors from children treated at Children’s Hospital Colorado. These samples are part of ongoing single-cell pediatric brain tumor banking that our group initiated a decade ago. The maturity of this resource, collected over a decade, provides us with the opportunity to perform well-powered outcome association studies. Samples are collected during routine surgery and immediately disaggregated to isolate single cells. These are then viably frozen in DMSO and banked for later use. We have tumors that cover the variety of subtypes in each of these diseases, as well as comprehensive clinical information on these cases, which will allow us to correlate molecular subtypes and research findings with these clinical measures. Here, we perform single-cell RNA-sequencing on 23 samples from patients with PHGG. In PHGG, we aim to understand the extent to which pediatric HGG stem like cells may differentiate into other cell types found in HGG tumors, or whether the non-stemlike cells may be derived from host tissue; whether gene expression is altered in host cells as the result of interactions with tumor stem cells; and the extent to which specific gene expression patterns among tumor cell subpopulations correlate with outcome measures such as mortality or event-free survival. These studies will significantly advance our understanding of disease biology and provide the detailed molecular and functional insights needed to identify new therapeutic targets for these biologically and clinically heterogeneous tumors.
Additional Sample Metadata Fieldsoutcome, molecular_characteristics, submitter_id, spinal_leptomeningeal_mets, submitter, scpca_project_id, participant_id
Alex’s Lemonade Stand Foundation for Childhood Cancer333 E. Lancaster Ave, #414, Wynnewood, PA 19096 USAPhone: 866.333.1213 • Fax: 610.649.3038