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Series GSE173958 Query DataSets for GSE173958
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
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.
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
Contributor(s) Simeonov KP
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Submission date May 05, 2021
Last update date Jun 11, 2021
Contact name Kamen P Simeonov
Organization name University of Pennsylvania
Street address 3800 Spruce St
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (24)
GSM5283482 Mouse1, Primary tumor, transcriptome
GSM5283483 Mouse1, Surgical site, transcriptome
GSM5283484 Mouse1, Peritoneal mets, transcriptome
BioProject PRJNA727607
SRA SRP318635

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE173958_RAW.tar 1.6 Gb (http)(custom) TAR (of MTX, TSV, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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