Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA727607 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2021-06-09 | GSE173958 | GEO
Project description: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 that 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.
| S-EPMC8782207 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE34280: Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Affymetrix SNP6 Arrays] GSE34355: Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Illumina Infinium HumanMethylation27 Beadchip v1.2] Refer to individual Series
2011-12-13 | E-GEOD-34356 | biostudies-arrayexpress
Project description:EMT in cancer has been associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However,direct in vivo evidence supporting this possibility is still lacking. By screening a large panel of cell surface markers, we identified the existence of multiple tumour subpopulations associated with different EMT stages from epithelial to completely mesenchymal states passing through intermediate hybrid states in skin and mammary primary tumours. Although all EMT subpopulations presented similar tumour propagating cell capacity, they displayed different , invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes defined by RNA-seq and ATAC-seq identified the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulateEMT transition states.
2018-02-15 | GSE110585 | GEO
Project description:EMT (epithelial-mesenchymal transition) in cancer has been associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However,direct in vivo evidence supporting this possibility is still lacking. By screening a large panel of cell surface markers, we identified the existence of multiple tumour subpopulations associated with different EMT stages from epithelial to completely mesenchymal states passing through intermediate hybrid states in skin and mammary primary tumours. Although all EMT subpopulations presented similar tumour propagating cell capacity, they displayed different, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes defined by RNA-seq and ATAC-seq identified the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulateEMT transition states.
2018-02-15 | GSE110584 | GEO
Project description:EMT in cancer has been associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However,direct in vivo evidence supporting this possibility is still lacking. By screening a large panel of cell surface markers, we identified the existence of multiple tumour subpopulations associated with different EMT stages from epithelial to completely mesenchymal states passing through intermediate hybrid states in skin and mammary primary tumours. Although all EMT subpopulations presented similar tumour propagating cell capacity, they displayed different , invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes defined by RNA-seq and ATAC-seq identified the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulateEMT transition states.
2018-02-15 | GSE110586 | GEO
Project description:Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection
| PRJNA555350 | ENA
Project description:Curcumin (diferuloylmethane) is the bioactive phenolic compound, and the mechanism by which curcumin exerts its anti-metastatic effects was comprehensive and diverse. Several studies reported the anti-metastasis effect of curcumin by its ability to modulate the epithelial-to-mesenchymal transition (EMT) process in different cancers, and the underlying molecular mechanism is poorly understood. EMT is a highly conserved biological process in which epithelial cells acquire mesenchymal-like characteristics by losing their cell-cell junctions and polarity deviating cellular mechanism towards cancer metastasis triggering cancer cells to escape from a primary site to distant locations causing spread of cancer to the entire system ultimately leading to death. In this perspective, we explored the anti-metastatic potential and mechanism of curcumin on the EMT process by establishing in-vitro EMT model using A549 cells induced by TGF-β1. Our results showed that curcumin inhibited EMT by regulating the expression of crucial mesenchymal markers such as MMP2, vimentin, and N-Cadherin. Besides, the transcriptional analysis revealed that curcumin treatment differentially regulated the expression of 75 genes in the NanoString n-counter platform. Further PPI (Protein-protein interaction) network and clusters analysis of differentially expressed genes (DEGs) revealed their involvement in essential biological processes. Altogether, the analysis gives a comprehensive overview of the anti-metastatic effect of curcumin in inhibiting TGF-β1 induced EMT in A549 cells.
2022-07-01 | GSE174129 | GEO
Project description:Comparison of gene expression between poorly metastatic HCT116 colon cancer cell line and the in-vivo derived metastatic E1 cell line, which has EMT (epithelial to mesenchymal transition) features. Each cell line has triplicate chips.
2011-03-01 | E-GEOD-13759 | biostudies-arrayexpress
Project description:Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell-type in terms of their origins and functional effects in vivo. Methods: Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen inducible Cre for cellular lineage tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Results: Lineage tracing with 4 additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin+ myofibroblasts reduces collagen production and scar formation after myocardial infarction. Periostin-traced myofibroblasts also revert back to a less activated state upon injury resolution. Conclusions: Our results define the myofibroblast as a periostin-expressing cell-type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21+ tissue-resident fibroblasts. Fluidigm C1 whole genome transcriptome analysis of lineage mapped cardiac myofibroblasts
2016-06-14 | E-GEOD-83337 | biostudies-arrayexpress