Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1071491 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We established a human liver organoid (HLO) based screening model for analyzing DILI pathology at organoid resolution. HLO contains polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNAseq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. By developing a 384 well based high-speed live imaging platform, we successfully developed a Liver organoid-based Toxicity screen (LoT) with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity. We functionally validated LoT with 238 marketed drugs at 4 different concentrations. LoT positively predicts genomic predisposition (CYP2C9*2) for Bosentan-induced cholestasis. Thus, LoT is a high-fidelity model for drug safety with a cost-effective platform, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications.
2020-10-18 | GSE141183 | GEO
Project description:“Direct to Drug” screening as a precision medicine tool in multiple myeloma
| PRJNA627346 | ENA
Project description:High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.
2023-05-19 | GSE227387 | GEO
Project description:High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.
2023-05-19 | GSE227391 | GEO
Project description:High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.
2023-05-19 | GSE227388 | GEO
Project description:Patient derived organoids (PDOs) closely resemble individual tumor biology. They are thus promising models for drug discovery and precision medicine. Here, we describe high-throughput imaging and automated image analysis of PDOs. We generated PDOs from colorectal cancer patients. Subsequently, we treated them with >500 substances to capture almost 6 million images by confocal microscopy. We developed a software framework to analyze how perturbations alter the organization of multicellular PDOs. Therewith, we observed a rich spectrum of reoccurring phenotypes. Targeting cellular processes, including signaling by MEK, GSK3 or CDKs, led to distinct architectural changes. Also, we detected compound-induced phenotypes only present in subsets of PDOs with specific molecular alterations. Finally, PDO response to anticancer drugs matched the clinical course of corresponding patients. The presented high-throughput imaging workflow and data allow compound profiling with complex multicellular organoid models for drug discovery and personalized medicine. We used microarrays to detail the global programme of gene expression underlying different lines of patient-derived colorectal cancer organoids.
2019-03-03 | GSE117548 | GEO
Project description:Matrigel, a mouse tumor extracellular matrix (ECM) protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal (GI) tissue-derived ECM hydrogels are a suitable substitute for Matrigel in GI organoid culture. We found that the development and function of GI organoids grown in GI ECM hydrogels are comparable or often superior to those in Matrigel. In addition, GI ECM hydrogels enabled long-term subculture and transplantation of GI organoids by providing GI tissue-mimetic microenvironments. Tissue-specific and age-related ECM profiles of GI ECM hydrogels that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that ECM hydrogels derived from decellularized GI tissues are an effective alternative to the current gold standard, Matrigel, and produce organoids suitable for GI disease modeling, drug development, and tissue regeneration.
2022-02-10 | PXD023694 | Pride