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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 09, 2021 |
| Title |
Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we recover ~380,000 CRISPR target sites and reconstruct dissemination of ~28,000 single cells across multiple metastatic sites. We find cells occupy a continuum of epithelial-to-mesenchymal transition (EMT) states. Metastatic potential peaks in rare, late-hybrid EMT states, which are aggressively selected from a predominately epithelial ancestral pool. The gene signatures of these late-hybrid EMT states are predictive of reduced survival in both human pancreatic and lung cancer patients, highlighting their relevance to clinical disease progression. Finally, we observe evidence for in vivo propagation of S100 family gene expression across clonally distinct metastatic subpopulations.
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| Overall design |
Single-cell RNA sequencing of transcriptomes and static plus evolving barcodes to capture lineage information from two mice with metastastic PDAC and from cultured cells
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| Contributor(s) |
Simeonov KP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 05, 2021 |
| Last update date |
Jun 11, 2021 |
| Contact name |
Kamen P Simeonov |
| E-mail(s) |
kamen.simeonov@gmail.com
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| Organization name |
University of Pennsylvania
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| Street address |
3800 Spruce St
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| GSM5283485 |
Mouse1, Liver, transcriptome |
| GSM5283486 |
Mouse1, Lung, transcriptome |
| GSM5283487 |
Mouse1, CTCs, transcriptome |
| GSM5283488 |
Mouse2, Primary tumor, transcriptome |
| GSM5283489 |
Mouse2, Peritoneal mets, transcriptome |
| GSM5283490 |
Mouse2, Liver, transcriptome |
| GSM5283491 |
Mouse2, Lung, transcriptome |
| GSM5283492 |
invitro, 5cell, transcriptome |
| GSM5283493 |
invitro, 100cell, transcriptome |
| GSM5283494 |
Mouse1, Primary tumor, lineage |
| GSM5283495 |
Mouse1, Surgical site, lineage |
| GSM5283496 |
Mouse1, Peritoneal mets, lineage |
| GSM5283497 |
Mouse1, Liver, lineage |
| GSM5283498 |
Mouse1, Lung, lineage |
| GSM5283499 |
Mouse1, CTCs, lineage |
| GSM5283500 |
Mouse2, Primary tumor, lineage |
| GSM5283501 |
Mouse2, Peritoneal mets, lineage |
| GSM5283502 |
Mouse2, Liver, lineage |
| GSM5283503 |
Mouse2, Lung, lineage |
| GSM5283504 |
invitro, 5cell, lineage |
| GSM5283505 |
invitro, 100cell, lineage |
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| Relations |
| BioProject |
PRJNA727607 |
| SRA |
SRP318635 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE173958_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of MTX, TSV, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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