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GSE133479

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Cancer avatars derived from genetically engineered pluripotent stem cells allow for longitudinal assessment of tumor development

Organism: Homo sapiens
Platform: GPL20301
Samples: 6
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Jun 28 2019
Last Updated: Mar 10 2020
Status: Public on Dec 10 2019
Contact: Matteo,,D'Antonio (UCSD)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA551582 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP212259

Summary

Many current cellular models aimed to elucidate cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a new cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that capture authentic cancer pathobiology. Orthotopic engraftment of the neural progenitor cells derived from hiPSCs introduced with tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) results in formation of brain tumors. As observed in GBM patient samples, these models harbor inter-tumor heterogeneity resembling different GBM molecular subtypes, and intra-tumor heterogeneity. Further, re-engraftment of these tumor cells generate tumors with features characteristic of patient samples and present mutation-dependent patterns of tumor evolution. Thus, these cancer avatar models provide a platform for a comprehensive longitudinal assessment of human tumor development as governed by molecular subtype mutations.

Overall Design

iGBM models (all in duplicates): TP53-/-;PDGFRAΔ8-9; PTEN-/-;NF1-/-; and controls

Analysis (2 steps)

View Data Processing
Processing steps for GSE133479
  1. RNA-seq reads were aligned to the human genome (hg19) with STAR 2.4.0h (outFilterMultimapNmax 20, outFilterMismatchNmax 999, outFilterMismatchNoverLmax 0.04, outFilterIntronMotifs RemoveNoncanonicalUnannotated, outSJfilterOverhangMin 6 6 6 6, seedSearchStartLmax 20, alignSJDBoverhangMin 1) using a gene database constructed from Gencode v19
  2. Reads that overlap with exon coordinates were counted using HTSeqcount (-s reverse -a 0 -t exon -i gene_id -m union)

Supplementary Files (1)

GSE133479_RAW.tar Download
GEO Samples (6)
GSM3910175 GSM3910176 GSM3910177 GSM3910178 GSM3910179 GSM3910180

Dataset Citations (1)

Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.
PMID 31992716 · 2020 · Nature communications
Tomoyuki Koga, Isaac A Chaim, Jorge A Benitez, Sebastian Markmiller, Alison D Parisian, Robert F Hevner, Kristen M Turner, Florian M Hessenauer, Matteo D'Antonio, Nam-Phuong D Nguyen, Shahram Saberi, Jianhui Ma, Shunichiro Miki, Antonia D Boyer, John Ravits, Kelly A Frazer, Vineet Bafna, Clark C Chen, Paul S Mischel, Gene W Yeo, Frank B Furnari

SRA Experiments (6) and Runs (6)

Total: 5865 MB
SRX6373786 SRP212259 RNA-Seq SINGLE
GSM3910175: smNPCWT_S1_L002; Homo sapiens; RNA-Seq
Sample: SRS5034603
BioProject: PRJNA551582
BioSample: SAMN12158273
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: ctrl
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: wildtype
Original files (1)
ctrl
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610546 51688863 2584443150 1033.75 smNPCWT_S1_L002_R1_001.fastq.gz, SRR9610546, SRR9610546.sralite SRA
SRX6373787 SRP212259 RNA-Seq SINGLE
GSM3910176: smNPCWT_S1_L003; Homo sapiens; RNA-Seq
Sample: SRS5034604
BioProject: PRJNA551582
BioSample: SAMN12158272
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: ctrl
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: wildtype
Original files (1)
ctrl
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610547 51764356 2588217800 1037.24 smNPCWT_S1_L003_R1_001.fastq.gz, SRR9610547, SRR9610547.sralite SRA
SRX6373788 SRP212259 RNA-Seq SINGLE
GSM3910177: smNPCT9A35_S3_L002; Homo sapiens; RNA-Seq
Sample: SRS5034605
BioProject: PRJNA551582
BioSample: SAMN12158271
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: TP53_null_PDGFRA_mut
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: TP53-/-;PDGFRA<delta>8-9
Original files (1)
TP53_null_PDGFRA_mut
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610548 50854974 2542748700 1017.86 smNPCT9A35_S3_L002_R1_001.fastq.gz, SRR9610548, SRR9610548.sralite SRA
SRX6373789 SRP212259 RNA-Seq SINGLE
GSM3910178: smNPCT9A35_S3_L003; Homo sapiens; RNA-Seq
Sample: SRS5034606
BioProject: PRJNA551582
BioSample: SAMN12158270
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: TP53_null_PDGFRA_mut
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: TP53-/-;PDGFRA<delta>8-9
Original files (1)
TP53_null_PDGFRA_mut
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610549 50888433 2544421650 1020.65 smNPCT9A35_S3_L003_R1_001.fastq.gz, SRR9610549, SRR9610549.sralite SRA
SRX6373790 SRP212259 RNA-Seq SINGLE
GSM3910179: smNPCP21C21_S2_L002; Homo sapiens; RNA-Seq
Sample: SRS5034607
BioProject: PRJNA551582
BioSample: SAMN12158269
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: PTEN_null_NF1_null
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: PTEN-/-;NF1-/-
Original files (1)
PTEN_null_NF1_null
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610550 43706160 2185308000 877.76 smNPCP21C21_S2_L002_R1_001.fastq.gz, SRR9610550, SRR9610550.sralite SRA
SRX6373791 SRP212259 RNA-Seq SINGLE
GSM3910180: smNPCP21C21_S2_L003; Homo sapiens; RNA-Seq
Sample: SRS5034608
BioProject: PRJNA551582
BioSample: SAMN12158268
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: PTEN_null_NF1_null
tissue: iPSC-derived induced glioblastoma (iGBM) model
cell type: iPSC-derived neural progenitor cells
iPSc passage: 35-45
differentiation day: 30
genotype: PTEN-/-;NF1-/-
Original files (1)
PTEN_null_NF1_null
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR9610551 43630983 2181549150 877.99 smNPCP21C21_S2_L003_R1_001.fastq.gz, SRR9610551, SRR9610551.sralite SRA

Linked Publications (1)

Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.
Nature communications · 2020

Data Files (12)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— smNPCP21C21_S2_L002_R1_001.fastq.gz RNA-Seq 877.8 MB link
— smNPCP21C21_S2_L002_R1_001.fastq.gz RNA-Seq 877.8 MB link
— smNPCP21C21_S2_L003_R1_001.fastq.gz RNA-Seq 878.0 MB link
— smNPCP21C21_S2_L003_R1_001.fastq.gz RNA-Seq 878.0 MB link
— smNPCT9A35_S3_L002_R1_001.fastq.gz RNA-Seq 1017.9 MB link
— smNPCT9A35_S3_L002_R1_001.fastq.gz RNA-Seq 1017.9 MB link
— smNPCT9A35_S3_L003_R1_001.fastq.gz RNA-Seq 1020.6 MB link
— smNPCT9A35_S3_L003_R1_001.fastq.gz RNA-Seq 1020.6 MB link
— smNPCWT_S1_L002_R1_001.fastq.gz RNA-Seq 1.0 GB link
— smNPCWT_S1_L002_R1_001.fastq.gz RNA-Seq 1.0 GB link
— smNPCWT_S1_L003_R1_001.fastq.gz RNA-Seq 1.0 GB link
— smNPCWT_S1_L003_R1_001.fastq.gz RNA-Seq 1.0 GB link