From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish
Abstract
:1. Introduction
2. From the Psychiatrist’s Couch
3. The Genetic Architecture of BD
4. Neurodevelopmental Anomalies in BD
5. The Promise of iPSCs
6. BD in a Dish
6.1. Neurodevelopmental Alterations in BD-derived iPSCs
6.2. Neuronal Activity in BD-derived iPSCs
6.3. Lithium-Response Pathways in BD-derived iPSCs
6.4. Select Changes in Gene Expression in BD-derived iPSCs
7. The Road Ahead: Promises, Caveats, and Challenges
7.1. Karyotype Analysis
7.2. Differentiation Capacity
7.3. Study Size
7.4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ref. | Source | Factors | Methods | N° | Auth | Karyo | Pluripotency |
---|---|---|---|---|---|---|---|
[63] | FB | OKSM | RV | ≥5 | nd | nd | ICC, EB and TriL |
[64] | FB | miR/NAM | LV | na | na | na | ICC |
[65] | FB | OKSM | RV | ≥3 | SNP | G-Band | ICC, PluriTest, EB and ScoC, Tera |
[66] | FB | OKSM | SV | 2 | nd | G-Band | ICC, TriL |
[67] | FB | miR/NAM | LV | na | na | na | ICC |
[68] | FB | OKSM | SV | 3 | nd | G-Band | ICC, EB and TriL |
[69] | LCL | OKSM, LIN28 | Epi | ≥3 | STRP | nd | ICC |
[70] | FB, LB | OKSM | Epi, LV, RV | 1–3 | SNP | nd | ICC, PluriTest, EB, Tera |
[71] | AP | OKSM | Epi | 1 | nd | nd | ICC, EB and TriL |
Ref. | Study Design | BD vs. Controls | Model | Major Cell Type(s) |
---|---|---|---|---|
[63] | BD I (LR)—control | 3 vs. 3 | iPSC | Forebrain, mixed glutamatergic—GABAergic neurons |
[64] | BD I—control | 12 vs. 6 | iNLC | NSC, NPC, neuronal-like cells |
[65] | Familial BD | 2 vs. 2 | iPSC | FACS-sorted NPCs, neurons |
[66] | BD I—control | 6 vs. 4 | iPSC | Hippocampal dentate gyrus-like granule neurons |
[67] | BD I—control | 1 vs. 1 5 vs. 3 | iPSC iNLC | NPC, NPC-derived neurons transdifferentiated neurons |
[68] | Familial BD | 4 vs. 4 | iPSC | PAX6-positive NPC, early and late cortical neurons |
[69] | BD I (LR-NR)—control | 3 vs. 3 vs. 4 | iPSC | Hippocampal dentate gyrus-like granule neurons |
[70] | BD I (LR-NR)—control—MDD—PD | 7 vs. 3 vs. 6 vs. 2 vs. 1 | iPSC | Forebrain, mixed glutamatergic—GABAergic neurons |
[71] | BD I—control | 6 vs. 4 | iPSC | Cortical stem and progenitor cells |
Ref. | Major Methods | Major Findings in BD-derived iPSCs |
---|---|---|
[63] | Microarray, Ca2+ transients | Ventralization, increased expression of membrane bound receptors and ion channels, Li reduces wave altered length amplitude and Ca2+ transients |
[64] | Morphology, Res-Imag | Cellular adhesion associates with clinical response to Li |
[65] | NanoString, RNA-seq, WCPC | Impaired early NPCs proliferation that is normalized by GSK3β inhibitor, altered WNT/GSK3β signaling and ion channel expression in NPCs |
[66] | RNA-seq, WCPC | Altered neuronal excitability, altered mitochondrial function and size, Li reduces hyperexcitability in LR donors and partly normalizes mitochondrial function |
[67] | qRT-PCR, NanoString, reporter assays | Upregulation of miR-34a in NPC and neurons, reducing miR-34a expression enhances dendritic elaboration and maturation of NPCs |
[68] | Microarray | Deregulation of receptor-mediated signaling. RNA metabolism, and protein trafficking in late neurons, upregulation of GAD1 |
[69] | WCPC | Neurons differ according to LR and NR, larger fast after-hyperpolarization |
[70] | Proteomics | Li-response pathway in BD acts through GSK3β-dependent CRMP2 phosphorylation to alter dendrite and dendritic spine formation, Ca2+ fluxes and neuronal activity |
[71] | RNA-seq, WCPC | Upregulation of immune-regulatory NLRP2, GABA- and dopamine signaling |
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Hoffmann, A.; Sportelli, V.; Ziller, M.; Spengler, D. From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish. Int. J. Mol. Sci. 2018, 19, 770. https://doi.org/10.3390/ijms19030770
Hoffmann A, Sportelli V, Ziller M, Spengler D. From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish. International Journal of Molecular Sciences. 2018; 19(3):770. https://doi.org/10.3390/ijms19030770
Chicago/Turabian StyleHoffmann, Anke, Vincenza Sportelli, Michael Ziller, and Dietmar Spengler. 2018. "From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish" International Journal of Molecular Sciences 19, no. 3: 770. https://doi.org/10.3390/ijms19030770
APA StyleHoffmann, A., Sportelli, V., Ziller, M., & Spengler, D. (2018). From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish. International Journal of Molecular Sciences, 19(3), 770. https://doi.org/10.3390/ijms19030770