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Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [CHIR]

ABSTRACT: Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [CHIR]

PROVIDER: PRJNA978588 | ENA |

REPOSITORIES: ENA

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Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [Toxicants]

Project description:Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [Toxicants]

| PRJNA978589 | ENA

Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells

Project description:Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells

| PRJNA978583 | ENA

Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [Toxicants]

Project description:Animal studies for embryotoxicity evaluation of potential therapeutics and environmental factors are complex, costly, and time-consuming. Often, studies are not of human relevance because of species differences. In the present study, we recapitulated the process of cardiomyogenesis in human induced pluripotent stem cells (hiPSCs) by modulation of the Wnt signaling pathway to identify a key cardiomyogenesis gene signature that can be applied to identify compounds and/or stress factors compromising the cardiomyogenesis process. Among the 23 tested teratogens and 16 non-teratogens, we identified three retinoids including 13-cis-retinoic acid that completely block the process of cardiomyogenesis in hiPSCs. Moreover, we have identified an early gene signature consisting of 31 genes and associated biological processes that are severely affected by the retinoids. To predict the inhibitory potential of teratogens and non-teratogens in the process of cardiomyogenesis we established the “Developmental Cardiotoxicity Index” (DCI_31g) that accurately differentiates teratogens and non-teratogens to do or do not affect the differentiation of hiPSCs to functional cardiomyocytes.

2023-06-06 | GSE233924 | GEO

Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells [CHIR]

2023-06-06 | GSE233925 | GEO

Identification of cardiac developmental toxicants in differentiated human induced pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-06 | GSE233926 | GEO

Transcriptomic characterization of C57BL/6 mouse embryonic stem cell differentiation and its modulation by developmental toxicants

2014-09-09 | GSE60174 | GEO

Classification of developmental toxicants in a human iPSC transcriptomics-based test

Project description:Classification of developmental toxicants in a human iPSC transcriptomics-based test

| PRJNA777253 | ENA

Classification of developmental toxicants in a human iPSC transcriptomics-based test

Project description:There is a great need for in vitro tests that identify developmental toxicants in relation to human oral doses and blood concentrations. In the present study, we used the hiPSC-based UKK-24h-test and analyzed genome-wide expression profiles of 23 known teratogens and 16 non-teratogens. All compounds were analyzed at the maximal plasma concentration (Cmax) and the 20-fold Cmax for a 24 h incubation period in three independent experiments. Using the 1,000 probe sets with the highest variability and including information on cytotoxicity, a penalized logistic regression based classifier (top-1,000 classifier) reached an AUC, accuracy, sensitivity, and specificity of 0.96, 0.92, 0.96 and 0.88, respectively to correctly classify the compounds as teratogens or non-teratogens. This top-1,000 classifier reached a higher AUC, accuracy and sensitivity than a second classifier (SPS-classifier), which used the number of significant probe sets to classify the compounds. At least, the SPS-classifier had a specificity of 1. Classification at 20-fold Cmax did not lead to better performance metrics than testing at 1-fold Cmax. Finally, inclusion of cytotoxicity information into the classifier clearly improved the performance metrics. In conclusion, although further optimization by additional readouts and inclusion of cell systems that model different developmental processes is required, the UKK-24h-test will support the early discovery-phase detection of human developmental toxicants already in its present form.

2022-06-24 | GSE187001 | GEO

Transcriptomic characterization of C57BL/6 mouse embryonic stem cell differentiation and its modulation by developmental toxicants

Project description:To develop an in vitro model for developmental toxicity testing, we characterized gene expression changes during mouse embryonic stem cell (mESC) differentiation and their modulation by developmental toxicants. C57BL/6 mESCs were allowed to differentiate spontaneously and global gene expression changes were studied using microarrays at at different time points after embryoid body (EB) formation. Develpmental toxicants tested include 2.0 mM monobutyl phthalate (MBP), 0.25 mM thalidomide (THD), and 1.0 mM valproic acid (VPA). RNA of control samples (unexposed) was collected at 0, 24, 48, 72, 96, 120 and 168 h after EB formation; RNA of compound-exposed samples were collected at 24 h after EB formation. Three replicates were included for each experimental condition.

2014-09-09 | E-GEOD-60174 | biostudies-arrayexpress

Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration

Project description:The in vitro test battery of the European research consortium ESNATS (‘novel stem cell-based test systems’) has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/ dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.

2017-02-07 | GSE94521 | GEO

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