The fate of cell reprogramming

Karagiannis, Peter; Yamanaka, Shinya

doi:10.1038/nmeth.3109

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…In efforts to create more relevant models, human neurons have become available through reprogramming skin or blood cells into a state in which the cells have the capability to self-replicate indefinitely and differentiate into many cell types including neurons [Karagiannis and Yamanaka 2014]. Previously, human iPSC-derived neurons have been evaluated to screen for neurotoxic compounds [Ryan, et al 2016].…”

Section: Discussionmentioning

confidence: 99%

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

et al. 2017

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The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy. We demonstrate differential sensitivity of neurons to mechanistically distinct classes of chemotherapeutics. We also show a dose-dependent reduction of electrical activity as measured by mean firing rate of the neurons following treatment with paclitaxel. We compared neurite outgrowth and cell viability of iPSC-derived cortical (iCell® Neurons) and peripheral (Peri.4U) neurons to cisplatin, paclitaxel and vincristine. Goshajinkigan, a Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but not oxaliplatin as measured by morphological phenotypes. Thus, we have demonstrated the utility of human iPSC-derived neurons as a useful model to distinguish drug class differences and for studies of a potential neuroprotectant for the prevention of chemotherapy-induced peripheral neuropathy.

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Section: Discussionmentioning

confidence: 99%

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

et al. 2017

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“…Induced pluripotent stem cells (iPSCs) (Takahashi et al, 2007) and techniques allowing their in vitro differentiation into various cell lines and tissues (reviewed by Karagiannis and Yamanaka, 2014;Yu et al, 2014) make it feasible to study and manipulate developmental pathways in human and non-human primate cells (Marchetto et al, 2013;Wunderlich et al, 2014). This is particularly important for chimpanzees and other apes, for which we do not have the same embryonic stem cell resources as we have for humans.…”

Section: The Era Of Human Development In a Dishmentioning

confidence: 99%

Genomic approaches to studying human-specific developmental traits

Franchini

Pollard

2015

Development

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Changes in developmental regulatory programs drive both disease and phenotypic differences among species. Linking human-specific traits to alterations in development is challenging, because we have lacked the tools to assay and manipulate regulatory networks in human and primate embryonic cells. This field was transformed by the sequencing of hundreds of genomes -human and non-humanthat can be compared to discover the regulatory machinery of genes involved in human development. This approach has identified thousands of human-specific genome alterations in developmental genes and their regulatory regions. With recent advances in stem cell techniques, genome engineering, and genomics, we can now test these sequences for effects on developmental gene regulation and downstream phenotypes in human cells and tissues.

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“…iPSCs were originally derived using genome-integrating vectors, such as retroviral and lentiviral vectors, to introduce the reprogramming factors into somatic cells [15][16][17]. To solve the mutagenesis problem, integration-free and safer methods to generate iPSCs have been reported, including (1) non-genome integrating vectors, such as adenoviruses, Sendai viruses, plasmids and episomal plasmid vectors, (2) genetic manipulation, such as transposons and Cre-loxP systems, (3) the introduction of mRNA and proteins of reprogramming transcription factors and (4) treatment with chemical compounds [19,20].…”

Section: Embryonic Renal Stem/progenitor Cells Differentiated From Plmentioning

confidence: 99%

“…These treatments combine diffusible factors (growth factors, cytokines and chemical compounds), cell-cell interactions (co-culture with cell lines) and positional cues (extracellular matrix) that ultimately regulate the gene expression, which together confer a specific cellular identity and function. Genetic and epigenetic manipulations using the overexpression of cDNA, small interfering RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA) have also been utilized to induce specific cell fates [19,20,[22][23][24].…”

Section: Mechanisms Of Cues For Directed Differentiation Of Pluripotementioning

confidence: 99%

“…Other research areas that utilize ESC/iPSC-derived renal lineage cells for clinical application or practical use include disease modelling, drug discovery and toxicology screening [19,20]. iPSC technology enables the creation of patient-or disease-specific iPSC lines that carry disease genotypes.…”

Section: Clinical Application and Practical Use Of Renal Stem Cellsmentioning

confidence: 99%

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