Ontology highlight
ABSTRACT:
PROVIDER: PRJNA616016 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11440959.fastq.gz | Fastqsanger.gz | |||
| SRR11440960.fastq.gz | Fastqsanger.gz | |||
| SRR11440961.fastq.gz | Fastqsanger.gz | |||
| SRR11440962.fastq.gz | Fastqsanger.gz | |||
| SRR11440963.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 29 |
Similar Datasets
Project description:Cancer is the second leading cause of death globally, and this is due primarily to metastatic dissemination to distal sites. Metastatic outgrowth requires that cancer cells delaminate from the primary tumor, intravasate, survive in circulation, extravasate, then migrate to and proliferate at a distal site. Recurrent genetic drivers of metastasis have remained elusive, suggesting that, unlike the initial steps of oncogenic transformation and primary tumor development, drivers of metastasis may be variable. Here, we develop a framework for interrogating pathways governing metastasis by applying CRISPR/Cas9-based forward genetic screening in a genetically defined tumor-organoid model of colorectal adenocarcinoma. We conduct in vitro screens for invasion and migration alongside orthotopic, in vivo screens for gain of metastatic potential in a syngeneic mouse model, identifying suppressors of metastasis both unique to the in vivo setting as well as common to both models. Specifically, we identify Ctnna1 and Bcl2l13 as bona fide metastasis suppressors acting through distinct mechanisms, with CTNNA1 loss promoting carcinoma cell invasion and migration through an atypical EMT-like mechanism, and BCL2L13 loss promoting cell survival after extracellular matrix detachment and non-cell-autonomous changes to macrophage polarization. Ultimately, this study provides a proof-of-principle that high-content forward genetic screening can be performed in tumor-organoid models in vivo and identifies novel regulators of colon cancer metastasis.
2025-07-21 | GSE237980 | GEO
Project description:Cancer is the second leading cause of death globally, and this is due primarily to metastatic dissemination to distal sites. Metastatic outgrowth requires that cancer cells delaminate from the primary tumor, intravasate, survive in circulation, extravasate, then migrate to and proliferate at a distal site. Recurrent genetic drivers of metastasis have remained elusive, suggesting that, unlike the initial steps of oncogenic transformation and primary tumor development, drivers of metastasis may be variable. Here, we develop a framework for interrogating pathways governing metastasis by applying CRISPR/Cas9-based forward genetic screening in a genetically defined tumor-organoid model of colorectal adenocarcinoma. We conduct in vitro screens for invasion and migration alongside orthotopic, in vivo screens for gain of metastatic potential in a syngeneic mouse model, identifying suppressors of metastasis both unique to the in vivo setting as well as common to both models. Specifically, we identify Ctnna1 and Bcl2l13 as bona fide metastasis suppressors acting through distinct mechanisms, with CTNNA1 loss promoting carcinoma cell invasion and migration through an atypical EMT-like mechanism, and BCL2L13 loss promoting cell survival after extracellular matrix detachment and non-cell-autonomous changes to macrophage polarization. Ultimately, this study provides a proof-of-principle that high-content forward genetic screening can be performed in tumor-organoid models in vivo and identifies novel regulators of colon cancer metastasis.
2025-07-21 | GSE263582 | GEO
Project description:Cancer is the second leading cause of death globally, and this is due primarily to metastatic dissemination to distal sites. Metastatic outgrowth requires that cancer cells delaminate from the primary tumor, intravasate, survive in circulation, extravasate, then migrate to and proliferate at a distal site. Recurrent genetic drivers of metastasis have remained elusive, suggesting that, unlike the initial steps of oncogenic transformation and primary tumor development, drivers of metastasis may be variable. Here, we develop a framework for interrogating pathways governing metastasis by applying CRISPR/Cas9-based forward genetic screening in a genetically defined tumor-organoid model of colorectal adenocarcinoma. We conduct in vitro screens for invasion and migration alongside orthotopic, in vivo screens for gain of metastatic potential in a syngeneic mouse model, identifying suppressors of metastasis both unique to the in vivo setting as well as common to both models. Specifically, we identify Ctnna1 and Bcl2l13 as bona fide metastasis suppressors acting through distinct mechanisms, with CTNNA1 loss promoting carcinoma cell invasion and migration through an atypical EMT-like mechanism, and BCL2L13 loss promoting cell survival after extracellular matrix detachment and non-cell-autonomous changes to macrophage polarization. Ultimately, this study provides a proof-of-principle that high-content forward genetic screening can be performed in tumor-organoid models in vivo and identifies novel regulators of colon cancer metastasis.
2025-07-21 | GSE263581 | GEO
Project description:Cancer is the second leading cause of death globally, and this is due primarily to metastatic dissemination to distal sites. Metastatic outgrowth requires that cancer cells delaminate from the primary tumor, intravasate, survive in circulation, extravasate, then migrate to and proliferate at a distal site. Recurrent genetic drivers of metastasis have remained elusive, suggesting that, unlike the initial steps of oncogenic transformation and primary tumor development, drivers of metastasis may be variable. Here, we develop a framework for interrogating pathways governing metastasis by applying CRISPR/Cas9-based forward genetic screening in a genetically defined tumor-organoid model of colorectal adenocarcinoma. We conduct in vitro screens for invasion and migration alongside orthotopic, in vivo screens for gain of metastatic potential in a syngeneic mouse model, identifying suppressors of metastasis both unique to the in vivo setting as well as common to both models. Specifically, we identify Ctnna1 and Bcl2l13 as bona fide metastasis suppressors acting through distinct mechanisms, with CTNNA1 loss promoting carcinoma cell invasion and migration through an atypical EMT-like mechanism, and BCL2L13 loss promoting cell survival after extracellular matrix detachment and non-cell-autonomous changes to macrophage polarization. Ultimately, this study provides a proof-of-principle that high-content forward genetic screening can be performed in tumor-organoid models in vivo and identifies novel regulators of colon cancer metastasis.
2025-07-21 | GSE263580 | GEO
Project description:Pooled genetic screening with CRISPR/Cas9 has enabled genome-wide high-resolution assignment of genes to phenotypes. To assess the effect of a given genetic perturbation, each sgRNA must be evaluated in hundreds of cells to overcome stochastic genetic drift and obtain robust results. In complex models that display particularly high heterogeneity, such as organoids or tumors transplanted into mice however, sufficient representation typically requires unreasonable scaling, thus preventing genome-wide screens at high resolution. Here we present CRISPR-StAR, a screening paradigm that overcomes intrinsic and extrinsic heterogeneity as well as genetic drift in bottlenecks by leveraging internal controls generated through activating sgRNAs only in half of the progenies of each cell. We use CRISPR-StAR to reveal in vivo-specific genetic dependencies in a genome-wide screen in mouse melanoma. Benchmarking to a conventional screening setup highlights the improved data quality this technology delivers. We anticipate CRISPR-StAR to set a new standard for genetic screening in complex models, foremost in vivo.
2024-11-05 | GSE262308 | GEO
Project description:Pooled genetic screening with CRISPR/Cas9 has enabled genome-wide high-resolution assignment of genes to phenotypes. To assess the effect of a given genetic perturbation, each sgRNA must be evaluated in hundreds of cells to overcome stochastic genetic drift and obtain robust results. In complex models that display particularly high heterogeneity, such as organoids or tumors transplanted into mice however, sufficient representation typically requires unreasonable scaling, thus preventing genome-wide screens at high resolution. Here we present CRISPR-StAR, a screening paradigm that overcomes intrinsic and extrinsic heterogeneity as well as genetic drift in bottlenecks by leveraging internal controls generated through activating sgRNAs only in half of the progenies of each cell. We use CRISPR-StAR to reveal in vivo-specific genetic dependencies in a genome-wide screen in mouse melanoma. Benchmarking to a conventional screening setup highlights the improved data quality this technology delivers. We anticipate CRISPR-StAR to set a new standard for genetic screening in complex models, foremost in vivo.
2024-11-05 | GSE262307 | GEO
Project description:The role of nutrient signaling processes in the fate decision of CD8 is incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.
2021-02-25 | GSE148681 | GEO
Project description:The role of nutrient signaling processes in the fate decision of CD8 are incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.
2021-02-25 | GSE160313 | GEO
Project description:The role of nutrient signaling processes in the fate decision of CD8 is incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.
2021-02-25 | GSE160218 | GEO