Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.
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
Nature communications · 2020 · Vol. 11 (1) · pp. 550
Abstract
Many cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that captures authentic cancer pathobiology. Orthotopic engraftment of the neural progenitor cells derived from hiPSCs that have been genome-edited to contain tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) results in formation of high-grade gliomas. Similar to patient-derived GBM, these models harbor inter-tumor heterogeneity resembling different GBM molecular subtypes, intra-tumor heterogeneity, and extrachromosomal DNA amplification. Re-engraftment of these primary tumor neurospheres generates secondary tumors with features characteristic of patient samples and present mutation-dependent patterns of tumor evolution. These cancer avatar models provide a platform for comprehensive longitudinal assessment of human tumor development as governed by molecular subtype mutations and lineage-restricted differentiation.
Linked datasets 2
Cancer avatars derived from genetically engineered pluripotent stem cells allow for longitudinal assessment of tumor development
Homo sapiens
12 data files
| File | Type | Size |
|---|---|---|
| smNPCP21C21_S2_L002_R1_001.fastq.gz | RNA-Seq | 877.8 MB |
| smNPCP21C21_S2_L003_R1_001.fastq.gz | RNA-Seq | 878.0 MB |
| smNPCT9A35_S3_L002_R1_001.fastq.gz | RNA-Seq | 1017.9 MB |
| smNPCT9A35_S3_L003_R1_001.fastq.gz | RNA-Seq | 1020.6 MB |
| smNPCWT_S1_L002_R1_001.fastq.gz | RNA-Seq | 1.0 GB |
| smNPCWT_S1_L003_R1_001.fastq.gz | RNA-Seq | 1.0 GB |
| SRR9610546_GSM3910175 | RNA-Seq | 1.0 GB |
| SRR9610547_GSM3910176 | RNA-Seq | 1.0 GB |
| SRR9610548_GSM3910177 | RNA-Seq | 1017.0 MB |
| SRR9610549_GSM3910178 | RNA-Seq | 1020.0 MB |
| SRR9610550_GSM3910179 | RNA-Seq | 877.0 MB |
| SRR9610551_GSM3910180 | RNA-Seq | 877.0 MB |
Cancer avatars derived from genetically engineered pluripotent stem cells allow for longitudinal assessment of tumor development
Homo sapiens
28 data files
| File | Type | Size |
|---|---|---|
| 17_1_1C_TK_possorted_genome_bam.bam | RNA-Seq | 1.6 GB |
| 17_1_1T_TK_possorted_genome_bam.bam | RNA-Seq | 4.9 GB |
| 17_1_2C_TK_possorted_genome_bam.bam | RNA-Seq | 1.6 GB |
| 17_1_2T_TK_possorted_genome_bam.bam | RNA-Seq | 5.3 GB |
| 17_1_3C_TK_possorted_genome_bam.bam | RNA-Seq | 1.3 GB |
| 17_1_3T_TK_possorted_genome_bam.bam | RNA-Seq | 6.7 GB |
| 17_2_1C_TK_possorted_genome_bam.bam | RNA-Seq | 13.9 GB |
| 17_2_1T_TK_possorted_genome_bam.bam | RNA-Seq | 1.7 GB |
| 17_2_2C_TK_possorted_genome_bam.bam | RNA-Seq | 11.3 GB |
| 17_2_2T_TK_possorted_genome_bam.bam | RNA-Seq | 1.9 GB |
| 17_2_3C_TK_possorted_genome_bam.bam | RNA-Seq | 12.0 GB |
| 17_2_3T_TK_possorted_genome_bam.bam | RNA-Seq | 3.7 GB |
| 3_5_1C_TK_possorted_genome_bam.bam | RNA-Seq | 5.0 GB |
| 3_7_1C_TK_possorted_genome_bam.bam | RNA-Seq | 10.9 GB |
| SRR9611927_GSM3910556 | RNA-Seq | 5.0 GB |
| SRR9611928_GSM3910557 | RNA-Seq | 4.9 GB |
| SRR9611929_GSM3910558 | RNA-Seq | 5.3 GB |
| SRR9611930_GSM3910559 | RNA-Seq | 6.7 GB |
| SRR9611931_GSM3910560 | RNA-Seq | 1.6 GB |
| SRR9611932_GSM3910561 | RNA-Seq | 1.6 GB |
| SRR9611933_GSM3910562 | RNA-Seq | 1.3 GB |
| SRR9611934_GSM3910563 | RNA-Seq | 10.9 GB |
| SRR9611935_GSM3910564 | RNA-Seq | 1.7 GB |
| SRR9611936_GSM3910565 | RNA-Seq | 1.9 GB |
| SRR9611937_GSM3910566 | RNA-Seq | 3.7 GB |
| SRR9611938_GSM3910567 | RNA-Seq | 13.9 GB |
| SRR9611939_GSM3910568 | RNA-Seq | 11.3 GB |
| SRR9611940_GSM3910569 | RNA-Seq | 12.0 GB |
Potentially related datasets 2
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| GSE133479 | GSE · GEO GEO ↗ | Cancer avatars derived from genetically engineered pluripotent stem cells allow for longitudinal assessment of tumor development |
| GSE133509 | GSE · GEO GEO ↗ | Cancer avatars derived from genetically engineered pluripotent stem cells allow for longitudinal assessment of tumor development |
Analysis pipelines 2
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE133479 RNA-seq Data Processing geo_data_processing | RNA-seq | 2 | GSE133479 |
| GSE133509 Data Processing geo_data_processing | — | 1 | GSE133509 |
Funding 9 grants
| Grant | Funder |
|---|---|
| P30 CA023100 | NCI NIH HHS (United States) |
| T32 GM145427 | NIGMS NIH HHS (United States) |
| T32 GM008666 | NIGMS NIH HHS (United States) |
| K12 GM068524 | NIGMS NIH HHS (United States) |
| R01 HL137223 | NHLBI NIH HHS (United States) |
| R01 HD085902 | NICHD NIH HHS (United States) |
| R01 GM114362 | NIGMS NIH HHS (United States) |
| R01 NS073831 | NINDS NIH HHS (United States) |
| R01 NS080939 | NINDS NIH HHS (United States) |