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| Recommendations in 2012 | Advancements in the past 3 years | Challenges remain |
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| Standardization of protocols |
(i) Optimizing reprogramming and differentiating methods
(ii) Efficient generation and validation of specific neural cell types
(iii) The importance of region and maturation state specific differentiation
(iv) Poorly defined regional identity | (i) Safe, integration-free, nonviral induction
(ii) Neurotransmitter and region specific protocols with efficacy >80%
(iii) Multiple model based studies
(iv) Combination of GWAS databases with iPSC/iNC observations | (i) Comparison of cells induced from different peripheral tissues
(ii) Utility of induced glial cells in psychiatric research |
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| Improving homogeneity |
(i) Detailed comparison of induced and source cells to reveal de novo genetic mutations
(ii) Multiple parallel cell lines from one donor
(iii) Epigenetic mapping during reprogramming and differentiation | (i) Vector integration-free, “safe” reprogramming methods
(ii) Reassuring results on chromosomal mutations
(iii) Average 3 cell lines/donor
(iv) Experiments and reviews comparing the available protocols | (i) Concerns on de novo CNV mutations and the neuronal genome
(ii) Contradictions regarding epigenetics
(iii) Little is that known about endogenous production of astrocytes |
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| Increasing statistical power |
(i) Increasing sample sizes
(ii) Careful selection and grouping of subjects
(iii) Detailed clinical and genetic characterization of subjects
(iv) Overthought diseased-control pairing | (i) Studies with whole genome sequencing and whole transcriptome profiling
(ii) Isogenic case-control comparison (new DNA editing techniques, twin studies) | (i) Increasing sample sizes
(ii) Reconsideration of patient grouping
(iii) Transparent, published case-control matching |
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| Improve reproducibility, resource sharing, and collaboration |
(i) Establishing rigorous, transparent, and reproducible methods
(ii) Detailed publication of protocols
(iii) Rapid sharing of cell lines, technologies, and best practices
(iv) Improving public-private partnership | (i) iPSC banks combined with gene banks
(ii) Commercially available iPSCs, iCell neurons, and knock-out cell lines with isogenic controls
(iii) Open access movements
(iv) Results usually correlated with postmortem and animal model findings | (i) Guidelines for validation
(ii) Criteria for cell characterization (markers, electrophysiological properties)
(iii) Poor publication of donor’s genotype, clinical features |
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| Towards large-scale studies |
(i) Decreasing protocol diversity
(ii) Validation assays for phenotypic comparison of derived cell lines | (i) Protocol diversity remains, but major steps towards large-scale production
(ii) Commercially available cells provide enough experimental material for high throughput assays | Personalized medicine requires reprogramming and differentiation by every single patient, which is still remarkably time-consuming and money consuming |
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| Careful patient selection, case-control matching |
(i) Subgrouping on the base of comprehensive genetic and clinical characterization
(ii) Linking genotype with molecular and cellular pathophysiology | (i) Isogenic case-control pairs provided by DNA editing techniques, twin studies
(ii) Pedigree-studies
(iii) DSM-5 reconsidered subcategories | Endophenotype-based subgrouping? |
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