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Ex-vivo screening platform to identify tumor-specific therapies

ABSTRACT: Ex-vivo screening platform to identify tumor-specific therapies

PROVIDER: PRJNA417676 | ENA |

REPOSITORIES: ENA

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Ex-vivo screening platform to identify tumor-specific therapies

Project description:We report the generation of a preclinical IBC patient-derived xenograft (PDX)-derived ex vivo tumor tissue model and show that it closely replicates the tissue architecture of the original PDX tumor harvested from mice and show that its genetic signature highly correlates with that of the original tumor. We used microarrays to evaluate the robustness and reproducibility of the method used to generate the ex vivo tumor tissue model and confirm its ability to recapitulate the essential features of the original tumor.

2018-04-07 | GSE106685 | GEO

EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform to identify cancer-specific epigenetic vulnerabilities

Project description:EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform to identify cancer-specific epigenetic vulnerabilities

| PRJNA727487 | ENA

High-throughput transcriptomics platform for screening hepatotoxicants

Project description:High-throughput transcriptomics platform for screening hepatotoxicants

| PRJNA638385 | ENA

Development of a split-toxin CRISPR screening platform to systematically identify upstream regulators of human myoblast fusion

Project description:Muscle defects are a common feature in human developmental disorders and often lead to severe functional impairment. These defects arise from intricate tissue crosstalk and rare genetic mutations, underscoring the need to systematically identify cell-autonomous mechanisms regulating human myogenesis. Despite the clinical significance, our understanding of human development remains limited, due in part to the absence of a scalable genetic approach to study this process. Here, we introduce a rationally designed high-throughput CRISPR screening platform that integrates human myoblast models, muscle-specific CRISPR knockout libraries, and a split-toxin strategy that acts as a functional readout for myoblast fusion—a fundamental step of human myogenesis. This screening strategy enables selection of CRISPR-induced fusion-defective myocytes in a quantifiable manner. Leveraging this platform, our initial genetic screen uncovered a large group of new hits essential for human myoblast fusion. The majority of these hits converge into 23 protein complexes, most of which have not previously been functionally linked to myogenesis in any species. Notably, mutations in 41 of our fusion screen hits cause human diseases presenting abnormal skeletal muscle morphology. Applying a new single-cell CRISPR & RNA-seq approach, we show that majority of these hits control human myoblast fusion as well as influence early-stage myogenic differentiation. Together, this work presents a new systematic approach to study human myogenesis and uncovers promising candidates governing human muscle differentiation and fusion. A broader application of this split-toxin based CRISPR screening platform would accelerate the study of cell-autonomous mechanisms of human muscle development and diseases at scale.

2025-10-24 | GSE293514 | GEO

Single-Cell Cas12a Platform for Screening and CRISPRi

Project description:Single-Cell Cas12a Platform for Screening and CRISPRi

| PRJNA1194560 | ENA

High-Throughput Transcriptomics Platform for Screening Environmental Chemicals

Project description:High-Throughput Transcriptomics Platform for Screening Environmental Chemicals

| PRJNA683595 | ENA

A safety screening platform for individualized cardiotoxicity assessment

Project description:A safety screening platform for individualized cardiotoxicity assessment

| PRJNA971626 | ENA

Development of a split-toxin CRISPR screening platform to systematically identify upstream regulators of human myoblast fusion

Project description:Development of a split-toxin CRISPR screening platform to systematically identify upstream regulators of human myoblast fusion

| PRJNA1244860 | ENA

A cyanobacterial screening platform for mutant variants of a Form II Rubisco

Project description:Cyanobacterial Form II Rubisco screening platform

| PRJEB79580 | ENA

A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity

Project description:This SuperSeries is composed of the SubSeries listed below. Disease, injury, and aging induce pathological reactive astrocyte states that contribute to neurodegeneration. Modulating reactive astrocytes therefore represents an attractive therapeutic strategy. Here, we describe the development of an astrocyte phenotypic screening platform for identifying chemical modulators of astrocyte reactivity. Leveraging this platform for chemical screening, we identify HDAC3 inhibitors as effective suppressors of pathological astrocyte reactivity. We demonstrate that HDAC3 inhibition reduces molecular and functional characteristics of reactive astrocytes in vitro. Transcriptional and chromatin mapping studies show that HDAC3 inhibition disarms pathological astrocyte gene expression and function while promoting the expression of genes associated with beneficial astrocytes. Administration of RGFP966, a small molecule HDAC3 inhibitor, blocks reactive astrocyte formation and promotes neuroprotection in vivo in mice. Collectively, these results establish a platform for discovering modulators of reactive astrocyte states, inform the mechanisms that control astrocyte reactivity, and demonstrate the therapeutic benefits of modulating astrocyte reactivity for neurodegenerative diseases.

2024-01-10 | GSE185215 | GEO

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