Mitochondrial ailments (Inak et al., 2017). Actually, among the essential advantages of iPSC-based models is the fact that they might let a precision medicine approach (Gibbs et al., 2018). Alternatively, iPSCs also hold disadvantages. Some studies reported that mtDNA MELAS mutations impair Trimethylamine N-oxide Endogenous Metabolite Cellular reprogramming to iPSCs (Yokota et al., 2015). Cellular fate-determination processes could also be affected, in unique neuronal and cardiac lineage commitment (Folmes et al., 2013; Hatakeyama et al., 2015; Yokota et al., 2017). This might be regarded as a possible readout for mitochondrial dysfunction, but in addition as a technical complication to generate patient iPSC derived cell lines. Moreover, the generation of iPSCs is expensive and time consuming. It is actually now apparent that unique iPSC lines is often extremely heterogeneous, thereby masking actual disease-associated phenotypes. Sadly, the reprogramming approach itself can also induce nuclear and mitochondrial DNA alterations (Pera, 2011; Perales-Clemente et al., 2016), and for that reason the genome of all iPSC lines requirements to become meticulously monitored.The differentiation of iPSCs is time-consuming and frequently very difficult in getting robust and homogenous differentiated progeny (Saha and Jaenisch, 2010), resulting in a small quantity of obtained differentiated cells that may limit the scalability as well as the high-throughput applications of iPSC-derived cells. Lastly, offered that iPSCs rejuvenate the state of mitochondria (Lisowski et al., 2018) along with the aging-associated epigenetic signature (Mertens et al., 2018), it has been suggested to circumvent the generation of iPSCs by using a direct reprogramming method (Vierbuchen et al., 2010). Within this strategy, patient-derived fibroblasts can be straight converted into neurons without having going by means of the state of iPSCs, thereby retaining the aging signature (Mertens et al., 2015; Victor et al., 2018). Nonetheless, also directly reprogrammed cells carry disadvantages as they must be generated newly continually and can’t be conveniently applied for genome editing.HIGH-CONTENT SCREENING APPLICATIONS TO STUDY MITOCHONDRIAL FUNCTIONSHigh-content screening (HCS) is defined as a cell-based phenotypic approach where readouts are imaged by multiplexed and automated microscopy (Zanella et al., 2010; Pegoraro and Misteli, 2017); this is also referred to as cellomics (Taylor, 2007). Because of the fast developments of technologies, probes and applications plus the upcoming field of iPSCs technology producing faithful cell Flufenoxuron Cancer disease models, the field of cellomics is now around the brink of catching up with the other mics approaches. Already in 2007 an HCS technique was developed combining evaluation with other cellular parameters measured in human liver carcinoma cells (HepG2) grown in a microfluidics device (Ye et al., 2007). Also performed in HepG2 cells an HCS assays has been described to screen drugs primarily based on six parameters among which and mitochondrial region (Persson et al., 2013) or intracellular redox state (Ye et al., 2007; Donato et al., 2012). A cellomics liver toxicity assay using iPSC-derived hepatocytes was lately published that focuses on drug development and toxicity testing, studying mitochondrial parameters as indicators of cellular health (Sirenko and Cromwell, 2018). Leonard et al. addressed a lot more technical elements of HCS application development combining the quantitative analysis of mitochondrial morphology and in living photoreceptor cells with supervised machine learning (Leona.
