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Project description:Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs)
| PRJNA898986 | ENA
Project description:Kinase inhibitors (KIs) are a promising alternative to traditional chemotherapeutics in the treatment of multiple cancer types. Unfortunately, some KIs induce cardiotoxicity as a severe side effect. To identify gene expression signatures that might be indicative of KI-induced cardiotoxicity, we generated two cardiomyocyte cell lines from induced pluripotent stem cells that we obtained from six healthy volunteers. Treatment of these cell lines with 41 FDA-approved drugs, i.e. 22 kinase inhibitors, 4 monoclonal antibodies, 4 anthracyclines, 8 cardiac acting and 3 non-cardiac acting drugs, allowed generation of 81 lists of differentially expressed genes.
2022-11-14 | GSE217423 | GEO
Project description:Kinase inhibitors (KIs) are a promising alternative to traditional chemotherapeutics in the treatment of multiple cancer types. Unfortunately, some kinase inhibitors induce cardiotoxicity as a severe side effect. To identify gene expression signatures that might be indicative of kinase inhibitor-induced cardiotoxicity, we generated six cardiomyocyte cell lines from induced pluripotent stem cells that we obtained from six healthy volunteers. Treatment of these cell lines with 54 FDA-approved drugs, i.e. 23 kinase inhibitors, 4 monoclonal antibodies, 4 anthracyclines, 7 cardiac acting and 16 non-cardiac acting drugs, allowed generation of 266 lists of differentially expressed genes. We subjected those lists to unsupervised and supervised algorithms to identify differentially expressed pathway activities associated with cardiotoxic responses.
2022-11-14 | GSE217421 | GEO
Project description:BACKGROUND:The discovery of induced pluripotent stem cells (iPSCs) opened the possibilities for reprogramming cells back to a pluripotent state. Because of no apparent ethical issues connected with donation and derivation of biomaterial, iPSCs are considered as a research alternative to ethically highly disputed human embryonic stem cells (hESCs). However, the unique character of iPSCs leads to numerous ethical considerations, which mainly concern the issue of donor information and consent for the use of biospecimen in research and drug evaluation. METHODS:For the purpose of this analysis, we conducted a review of the literature in the PubMed/MEDLINE and Web of Science databases. The search algorithm led to the identification of 1461 results. After removing duplicates and screening of title and abstract, 90 articles were found to be relevant to the study's objective. Full texts of these articles were apprised and 62 articles were excluded at this step for not properly addressing the study's objective. In the final step, 28 articles were included in the analysis. Analyzed were both research and non-research manuscripts published in peer-reviewed journals. RESULTS:In the case of iPSC research, the information process should be guided by general frameworks established for research on human subjects but also by specific characteristics of iPSCs. We determined four main domains and 12 thematic subdomains that should be included in donor information. Our results show that majority of authors agree to the content of information with regard to the areas of general information, storage of cells, and protection of privacy. Two main issues that are discussed in the literature are donor's consent for use in future studies and the process of donor information. CONCLUSIONS:Given the unique character of iPSCs and the possibility of their various uses in the future, the content of donor information should contain specific information central to iPSC research. Effective methods of communicating information to donors should combine written and oral information with the possible use of multimedia.
| S-EPMC7083011 | biostudies-literature
Project description:The discovery of induced pluripotent stem cells (iPSCs) has made an invaluable contribution to the field of regenerative medicine, paving way for identifying the true potential of human embryonic stem cells (ESCs). Since the controversy around ethicality of ESCs continue to be debated, iPSCs have been used to circumvent the process around destruction of the human embryo. The use of iPSCs have transformed biological research, wherein increasing number of studies are documenting nuclear reprogramming strategies to make them beneficial models for drug screening as well as disease modelling. The flexibility around the use of iPSCs include compatibility to non-invasive harvesting, and ability to source from patients with rare diseases. iPSCs have been widely used in cardiac disease modelling, studying inherited arrhythmias, neural disorders including Alzheimer's disease, liver disease, and spinal cord injury. Extensive research around identifying factors that are involved in maintaining the identity of ESCs during induction of pluripotency in somatic cells is undertaken. The focus of the current review is to detail all the clinical translation research around iPSCs and the strength of its ever-growing potential in the clinical space.
| S-EPMC8467501 | biostudies-literature
Project description:Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs) [Conv-GEO-Depot]
| PRJNA898988 | ENA
Project description:Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs) [DGE-GEO-Depot]
| PRJNA898990 | ENA
Project description:The systematic generation of neurons from patients with neurological disorders can provide important insights into disease pathology, progression and mechanism. This review will discuss recent progress in modeling neurodegenerative and neurodevelopmental diseases using induced pluripotent stem cells (iPSCs) and highlight some of the current challenges in the field. Combined with other technologies previously used to study brain disease, iPSC modeling has the promise to influence modern medicine on several fronts: early diagnosis, drug development and effective treatment.
| S-EPMC4447776 | biostudies-literature
Project description:MicroRNAs (miRNAs) are a newly discovered endogenous class of small noncoding RNAs that play important posttranscriptional regulatory roles by targeting mRNAs for cleavage or translational repression. Accumulating evidence now supports the importance of miRNAs for human embryonic stem cell (hESC) self-renewal, pluripotency, and differentiation. However, with respect to induced pluripotent stem cells (iPSC), in which embryonic-like cells are reprogrammed from adult cells using defined factors, the role of miRNAs during reprogramming has not been well-characterized. Determining the miRNAs that are associated with reprogramming should yield significant insight into the specific miRNA expression patterns that are required for pluripotency. To address this lack of knowledge, we use miRNA microarrays to compare the "microRNA-omes" of human iPSCs, hESCs, and fetal fibroblasts. We confirm the presence of a signature group of miRNAs that is up-regulated in both iPSCs and hESCs, such as the miR-302 and 17-92 clusters. We also highlight differences between the two pluripotent cell types, as in expression of the miR-371/372/373 cluster. In addition to histone modifications, promoter methylation, transcription factors, and other regulatory control elements, we believe these miRNA signatures of pluripotent cells likely represent another layer of regulatory control over cell fate decisions, and should prove important for the cellular reprogramming field.
| S-EPMC3135181 | biostudies-literature
Project description:Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells.
| S-EPMC3795682 | biostudies-literature