Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence

Ulrich Sauerzopf, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak-Rieder, Harald Sitte, Matthäus Willeit, Ulrich Sauerzopf, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak-Rieder, Harald Sitte, Matthäus Willeit

Abstract

Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.

Keywords: bipolar disorder; dopamine; induced neuron; induced pluripotent stem cell; neuronal progenitor cell; schizophrenia.

© 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

References

    1. Alda, M. (2015) Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol. Psychiatr., 20, 661–670.
    1. Batalla, A. , Bargalló, N. , Gassó, P. , Molina, O. , Pareto, D. , Mas, S. , Roca, J. , Bernardo, M. et al (2015) Apoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic‐naive first‐episode schizophrenia and healthy controls. Transl. Psychiat., 5, e626.
    1. Bavamian, S. , Mellios, N. , Lalonde, J. , Fass, D.M. , Wang, J. , Sheridan, S.D. , Madison, J.M. , Zhou, F. et al (2015) Dysregulation of miR‐34a links neuronal development to genetic risk factors for bipolar disorder. Mol. Psychiatr., 20, 573–584.
    1. Brennand, K.J. & Gage, F.H. (2011) Concise review: the promise of human induced pluripotent stem cell‐based studies of schizophrenia. Stem Cells, 29, 1915–1922.
    1. Brennand, K.J. , Simone, A. , Jou, J. , Gelboin‐Burkhart, C. , Tran, N. , Sangar, S. , Li, Y. , Mu, Y. et al (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473, 221–225.
    1. Brennand, K. , Savas, J.N. , Kim, Y. , Tran, N. , Simone, A. , Hashimoto‐Torii, K. , Beaumont, K.G. , Kim, H.J. et al (2015) Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatr., 20, 361–368.
    1. Caiazzo, M. , Dell'Anno, M.T. , Dvoretskova, E. , Lazarevic, D. , Taverna, S. , Leo, D. , Sotnikova, T.D. , Menegon, A. et al (2011) Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature, 476, 224–227.
    1. Carlsson, A. , Lindqvist, M. & Magnusson, T. (1957) 3,4‐Dihydroxyphenylalanine and 5‐Hydroxytryptophan as Reserpine Antagonists. Nature, 180, 1200.
    1. Chambers, S.M. , Fasano, C.A. , Papapetrou, E.P. , Tomishima, M. , Michael, S. & Studer, L. (2009) Highly efficient neural Conversion of human ES and iPSC cells by dual inhibition of SMAD signaling. Nat. Biotechnol., 27, 275–280.
    1. Chen, H. , DeLong, C. , Bame, M. , Rajapakse, I. , Herron, T. , McInnis, M. & O'shea, K. (2014) Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl. Psychiat., 4, e375.
    1. Chiang, C. , Su, Y. , Wen, Z. , Yoritomo, N. , Ross, C. , Margolis, R. , Song, H. & Ming, G. (2011) Integration‐free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol. Psychiatr., 16, 358.
    1. Ciliax, B. , Drash, G.W. , Staley, J.K. , Haber, S. , Mobley, C.J. , Miller, G.W. , Mufson, E.J. , Mash, D.C. et al (1999) Immunocytochemical localization of the dopamine transporter in human brain. J. Comp. Neurol., 409, 38–56.
    1. Cipriani, A. , Hawton, K. , Stockton, S. & Geddes, J.R. (2013) Lithium in the prevention of suicide in mood disorders: updated systematic review and meta‐analysis. Brit. Med. J., 346, 1–13.
    1. D'Aiuto, L. , Prasad, K.M. , Upton, C.H. , Viggiano, L. , Milosevic, J. , Raimondi, G. , McClain, L. , Chowdari, K. et al (2015) Persistent infection by HSV‐1 is associated with changes in functional architecture of iPSC‐derived neurons and brain activation patterns underlying working memory performance. Schizophrenia Bull., 41, 123–132.
    1. Duan, J. (2015) Path from schizophrenia genomics to biology: gene regulation and perturbation in neurons derived from induced pluripotent stem cells and genome editing. Neurosci. Bull., 31, 113–127.
    1. Eichler, E.E. , Flint, J. , Gibson, G. , Kong, A. , Leal, S.M. , Moore, J.H. & Nadeau, J.H. (2010) How should we solve the problem of “missing heritability” in complex diseases? Nat. Rev. Genet., 11, 446–450.
    1. Fan, Y. , Abrahamsen, G. , Mills, R. , Calderón, C.C. , Tee, J.Y. , Leyton, L. , Murrell, W. , Cooper‐White, J. et al (2013) Focal adhesion dynamics are altered in schizophrenia. Biol. Psychiat., 74, 418–426.
    1. Fasano, C.A. , Chambers, S.M. , Lee, G. , Tomishima, M. & Studer, L. (2010) Efficient derivation of functional floor plate tissue form human embryonic stem cells. Cell Stem Cell, 6, 336–347.
    1. Fournier, M. , Ferrari, C. , Baumann, P.S. , Polari, A. , Monin, A. , Bellier‐Teichmann, T. , Wulff, J. , Pappan, K.L. et al (2014) Impaired metabolic reactivity to oxidative stress in early psychosis patients. Schizophrenia Bull., 40, 973–983.
    1. Hartley, B. , Tran, N. , Ladran, I. , Reggio, K. & Brennand, K. (2015) Dopaminergic differentiation of schizophrenia hiPSCs. Mol. Psychiatr., 20, 549–550.
    1. Hashimi, S.T. , Fulcher, J.A. , Chang, M.H. , Gov, L. , Wang, S. & Lee, B. (2009) MicroRNA profiling identifies miR‐34a and miR‐21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation. Blood, 114, 404–414.
    1. Hashimoto‐Torii, K. , Torii, M. , Fujimoto, M. , Nakai, A. , El Fatimy, R. , Mezger, V. , Ju, M.J. , Ishii, S. et al (2014) Roles of heat shock factor 1 in neuronal response to fetal environmental risks and its relevance to brain disorders. Neuron, 82, 560–572.
    1. Hook, V. , Brennand, K.J. , Kim, Y. , Toneff, T. , Funkelstein, L. , Lee, K.C. , Ziegler, M. & Gage, F.H. (2014) Human iPSC neurons display activity‐dependent neurotransmitter secretion: aberrant catecholamine levels in schizophrenia neurons. Stem Cell Rep., 3, 531–538.
    1. Howes, O.D. , Kambeitz, J. , Kim, E. , Stahl, D. , Slifstein, M. , Abi‐Dargham, A. & Kapur, S. (2012) The nature of dopamine dysfunction in schizophrenia and what this means for treatment: meta‐analysis of imaging studies. Arch. Gen. Psychiat., 69, 776–786.
    1. Howes, O. , McCutcheon, R. & Stone, J. (2015) Glutamate and dopamine in schizophrenia: an update for the 21st century. J. Psychopharmacol., 29, 97–115.
    1. Hu, K. (2014) Vectorology and factor delivery in induced pluripotent stem cell reprogramming. Stem Cells Dev., 23, 1301–1315.
    1. Jacobs, B.M. (2015) A dangerous method? The use of induced pluripotent stem cells as a model for schizophrenia. Schizophr. Res., 168, 563–568.
    1. Jones, P. (2013) Adult mental health disorders and their age at onset. Brit. J. Psychiat., 202, s5–s10.
    1. Jones, C. , Watson, D. & Fone, K. (2011) Animal models of schizophrenia. Brit. J. Pharmacol., 164, 1162–1194.
    1. Kantor, L. , Park, Y.H. , Wang, K.K. & Gnegy, M.E. (2002) Enhanced amphetamine‐mediated dopamine release develops in PC12 cells after repeated amphetamine treatment. Eur. J. Pharmacol., 451, 27–35.
    1. Keshaban, M.I. , Anderson, S. & Pettegrew, J.W. (1994) Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited. J. Psychiatr. Res., 28, 239–265.
    1. Kessler, R.C. , Berglund, P. , Demler, O. , Jin, R. , Merikangas, K.R. & Walters, E.E. (2005) Lifetime prevalence and age‐of‐onset distributions of DSM‐IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiat., 62, 593–602.
    1. Kim, K. , Doi, A. , Wen, B. , Ng, K. , Zhao, R. , Cahan, P. , Kim, J. , Aryee, M. et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature, 467, 285–290.
    1. Kim, K. , Zhao, R. , Doi, A. , Ng, K. , Unternaehrer, J. , Cahan, P. , Hongguang, H. , Loh, Y.‐H. et al (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat. Biotechnol., 29, 1117–1119.
    1. Kriks, S. , Shim, J.‐W. , Piao, J. , Ganat, Y.M. , Wakeman, D.R. , Xie, Z. , Carrillo‐Reid, L. , Auyeung, G. et al (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson/'s disease. Nature, 480, 547–551.
    1. Kyttälä, A. , Moraghebi, R. , Valensisi, C. , Kettunen, J. , Andrus, C. , Pasumarthy, K.K. , Nakanishi, M. , Nishimura, K. et al (2016) Genetic variability overrides the impact of parental cell type and determines iPSC differentiation potential. Stem Cell Rep., 6, 200–212.
    1. Lancaster, M.A. & Knoblich, J.A. (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science, 345, 1247125.
    1. Lancaster, M.A. , Renner, M. , Martin, C.‐A. , Wenzel, D. , Bicknell, L.S. , Hurles, M.E. , Homfray, T. , Penninger, J.M. et al (2013) Cerebral organoids model human brain development and microcephaly. Nature, 501, 373–379.
    1. Laurelle, M. (2000) The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res. Rev., 31, 371–384.
    1. Lee, I.S. , Carvalho, C.M. , Douvaras, P. , Ho, S.‐M. , Hartley, B.J. , Zuccherato, L.W. , Ladran, I.G. , Siegel, A.J. et al (2015) Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient‐derived hiPSC neural cells. NPJ Schizophr., 1, 15019.
    1. Li, H. , Collado, M. , Villasante, A. , Strati, K. , Ortega, S. , Cañamero, M. , Blasco, M.A. & Serrano, M. (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature, 460, 1136–1139.
    1. Lindsay, E.A. , Morris, M.A. , Gos, A. , Nestadt, G. , Wolyniec, P.S. , Lasseter, V.K. , Shprintzen, R. , Antonarakis, S.E. et al (1995) Schizophrenia and chromosomal deletions within 22q11. 2. Am. J. Hum. Genet., 56, 1502.
    1. Madison, J.M. , Zhou, F. , Nigam, A. , Hussain, A. , Barker, D.D. , Nehme, R. , van der Ven, K. , Hsu, J. et al (2015) Characterization of bipolar disorder patient‐specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities. Mol. Psychiatr., 20, 703–717.
    1. Mahmoudi, S. & Brunet, A. (2012) Aging and reprogramming: a two‐way street. Curr. Opin. Cell Biol., 24, 744–756.
    1. Manolio, T.A. , Collins, F.S. , Cox, N.J. , Goldstein, D.B. , Hindorff, L.A. , Hunter, D.J. , McCarthy, M.I. , Ramos, E.M. et al (2009) Finding the missing heritability of complex diseases. Nature, 461, 747–753.
    1. Marchetto, M.C. & Gage, F.H. (2012) Modeling brain disease in a dish: really? Cell Stem Cell, 10, 642–645.
    1. Marchetto, M.C. & Gage, F.H. (2014) Your brain under the microscope: the promise of stem cells. Cerebrum, 1, 2014:1. eCollection.
    1. Marchetto, M.C. , Winner, B. & Gage, F.H. (2010) Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases. Hum. Mol. Genet., 19, R71–R76.
    1. Mariani, J. , Coppola, G. , Zhang, P. , Abyzov, A. , Provini, L. , Tomasini, L. , Amenduni, M. , Szekely, A. et al (2015) FOXG1‐Dependent dysregulation of GABA/Glutamate neuron differentiation in autism spectrum disorder. Cell, 162, 375–390.
    1. Mertens, J. , Wang, Q.‐W. , Kim, Y. , Diana, X.Y. , Pham, S. , Yang, B. , Zheng, Y. , Diffenderfer, K.E. et al (2015) Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature, 527, 95–99.
    1. Millar, J.K. , Wilson‐Annan, J.C. , Anderson, S. , Christie, S. , Taylor, M.S. , Semple, C.A. , Devon, R.S. , St Clair, D.M. et al (2000) Disruption of two novel genes by a translocation co‐segregating with schizophrenia. Hum. Mol. Genet., 9, 1415–1423.
    1. Miller, J.D. , Ganat, Y.M. , Kishinevsky, S. , Bowman, R.L. , Liu, B. , Tu, E.Y. , Mandal, P.K. , Vera, E. et al (2013) Human iPSC‐based modeling of late‐onset disease via progerin‐induced aging. Cell Stem Cell, 13, 691–705.
    1. Murai, K. , Sun, G. , Ye, P. , Tian, E. , Yang, S. , Cui, Q. , Sun, G. , Trinh, D. et al (2016) The TLX‐miR‐219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model. Nat. Commun., 7, 10965.
    1. Murray, G. , Jones, P. , Moilanen, K. , Veijola, J. , Miettunen, J. , Cannon, T. & Isohanni, M. (2006) Infant motor development and adult cognitive functions in schizophrenia. Schizophr. Res., 81, 65–74.
    1. van Os, J. & Kapur, S. (2009) Schizophrenia. Lancet, 374, 335–345.
    1. O'shea, K.S. & McInnis, M.G. (2016) Neurodevelopmental origins of bipolar disorder: iPSC models. Mol. Cell Neurosci., 73, 63–83.
    1. Park, Y.H. , Kantor, L. , Wang, K.K. & Gnegy, M.E. (2002) Repeated, intermittent treatment with amphetamine induces neurite outgrowth in rat pheochromocytoma cells (PC12 cells). Brain Res., 951, 43–52.
    1. Park, Y.H. , Kantor, L. , Guptaroy, B. , Zhang, M. , Wang, K.K. & Gnegy, M.E. (2003) Repeated amphetamine treatment induces neurite outgrowth and enhanced amphetamine‐stimulated dopamine release in rat pheochromocytoma cells (PC12 cells) via a protein kinase C‐and mitogen activated protein kinase‐dependent mechanism. J. Neurochem., 87, 1546–1557.
    1. Passeri, E. , Wilson, A.M. , Primerano, A. , Kondo, M.A. , Sengupta, S. , Srivastava, R. , Koga, M. , Obie, C. et al (2015) Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: utility in uncovering cellular deficits in mental illness‐associated chromosomal abnormalities. Neurosci. Res., 101, 57–61.
    1. Paulsen Bda, S. , de Moraes Maciel, R. , Galina, A. , Souza da Silveira, M. , dos Santos Souza, C. , Drummond, H. , Pozzatto, E.N. , Silva, H. Jr et al (2012) Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient. Cell Transplant., 21, 1547–1559.
    1. Paulsen Bda, S. , Cardoso, S.C. , Stelling, M.P. , Cadilhe, D.V. & Rehen, S.K. (2014) Valproate reverts zinc and potassium imbalance in schizophrenia‐derived reprogrammed cells. Schizophr. Res., 154, 30–35.
    1. Pedrosa, E. , Sandler, V. , Shah, A. , Carroll, R. , Chang, C. , Rockowitz, S. , Guo, X. , Zheng, D. et al (2011) Development of patient‐specific neurons in schizophrenia using induced pluripotent stem cells. J. Neurogenet., 25, 88–103.
    1. Pfisterer, U. , Kirkeby, A. , Torper, O. , Wood, J. , Nelander, J. , Dufour, A. , Björklund, A. , Lindvall, O. et al (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc. Natl. Acad. Sci. USA, 108, 10343–10348.
    1. Prabakaran, S. , Swatton, J.E. , Ryan, M.M. , Huffaker, S.J. , Huang, J.T.J. , Griffin, J.L. , Wayland, M. , Freeman, T. et al (2004) Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol. Psychiatr., 9, 684–697.
    1. Psychiatric Genetics Consortium , Schizophrenia Working Group (2014) Biological insights from 108 schizophrenia‐associated genetic loci. Nature, 511, 421–427.
    1. Qian, X. , Nguyen, H. , Song, M. , Hadiono, C. , Hammack, C. , Hamersky, G. , Jacob, F. , Zhong, C. et al (2016) Brain‐Region‐Specific organoids using mini‐bioreactors for modeling ZIKV exposure. Cell, 165, 1238–1254.
    1. Raab, S. , Klingenstein, M. , Liebau, S. & Linta, L. (2014) A comparative view on human somatic cell sources for ipsc generation. Stem Cells Int., 2014, 768391.
    1. Rajasekaran, A. , Venkatasubramanian, G. , Berk, M. & Debnath, M. (2015) Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci. Biobehav. R., 48, 10–21.
    1. Robicsek, O. , Karry, R. , Petit, I. , Salman‐Kesner, N. , Müller, F. , Klein, E. , Aberdam, D. & Ben‐Shachar, D. (2013) Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle‐derived induced pluripotent stem cells of schizophrenia patients. Mol. Psychiatr., 18, 1067–1076.
    1. Saha, S. , Chant, D. , Welham, J. & McGrath, J. (2005) A systematic review of the prevalence of schizophrenia. PLoS Med., 2, e141.
    1. Schneider, K. (1957) Primary & secondary symptoms in schizophrenia. Fortschr. Neurol. Psyc., 25, 487–490.
    1. Sekar, A. , Bialas, A.R. , de Rivera, H. , Davis, A. , Hammond, T.R. , Kamitaki, N. , Tooley, K. , Presumey, J. et al (2016) Schizophrenia risk from complex variation of complement component 4. Nature, 530, 177–183.
    1. Serra, G. , Koukopoulos, A. , De Chiara, L. , Napoletano, F. , Koukopoulos, A.E. , Curto, M. , Manfredi, G. , Faedda, G. et al (2015) Features preceding diagnosis of bipolar versus major depressive disorders. J. Affect. Disorders, 173, 134–142.
    1. Smoller, J.W. & Finn, C.T. (2003) Family, twin, and adoption studies of bipolar disorder In AmericanJournal Medical Genetics Part C: SeminarsMedicalGenetics. 15, 48–58.
    1. Srikanth, P. & Young‐Pearse, T.L. (2014) Stem cells on the brain: modeling neurodevelopmental and neurodegenerative diseases using human induced pluripotent stem cells. J. Neurogenet., 28, 5–29.
    1. Steinkellner, T. , Mus, L. , Eisenrauch, B. , Constantinescu, A. , Leo, D. , Konrad, L. , Rickhag, M. , Sørensen, G. et al (2014) In vivo amphetamine action is contingent on αCaMKII. Neuropsychopharmacol., 39, 2681–2693.
    1. Sullivan, P.F. , Kendler, K.S. & Neale, M.C. (2003) Schizophrenia as a complex trait: evidence from a meta‐analysis of twin studies. Arch. Gen. Psychiat., 60, 1187–1192.
    1. Takahashi, K. & Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.
    1. Takahashi, K. , Tanabe, K. , Ohnuki, M. , Narita, M. , Ichisaka, T. , Tomoda, K. & Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.
    1. Tandon, R. , Nasrallah, H.A. & Keshavan, M.S. (2009) Schizophrenia”, just the facts” 4. Clinical features and conceptualization. Schizophr. Res., 110, 1–23.
    1. Topol, A. , English, J. , Flaherty, E. , Rajarajan, P. , Hartley, B. , Gupta, S. , Desland, F. , Zhu, S. et al (2015) Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients. Transl. Psychiat., 5, e662.
    1. Topol, A. , Zhu, S. , Hartley, B.J. , English, J. , Hauberg, M.E. , Tran, N. , Rittenhouse, C.A. , Simone, A. et al (2016) Dysregulation of miRNA‐9 in a subset of Schizophrenia patient‐derived neural progenitor cells. Cell Rep., 15, 1024–1036.
    1. Tran, N.N. , Ladran, I.G. & Brennand, K.J. (2013) Modeling Schizophrenia Using induced pluripotent Stem cell–Derived and Fibroblast‐induced neurons. Schizophrenia Bull., 39, 4–10.
    1. Trokovic, R. , Weltner, J. , Noisa, P. , Raivo, T. & Otonkoski, T. (2015) Combined negative effect of donor age and time in culture on the reprogramming efficiency into induced pluripotent stem cells. Stem Cell Res., 15, 254–262.
    1. Valvezan, A.J. & Klein, P.S. (2012) GSK‐3 and Wnt signaling in neurogenesis and bipolar disorder. Front. Mol. Neurosci., 5, 1–13.
    1. Van Rossum, J. (1966) The significance of dopamine‐receptor blockade for the mechanism of action of neuroleptic drugs. Arch. Int. Pharmacod. T., 160, 492.
    1. Vaskova, E. , Stekleneva, A. , Medvedev, S. & Zakian, S. (2013) Epigenetic memory” phenomenon in induced pluripotent stem cells. Acta Naturae, 5, 15–21.
    1. Vierbuchen, T. , Ostermeier, A. , Pang, Z.P. , Kokubu, Y. , Südhof, T.C. & Wernig, M. (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463, 1035–1041.
    1. Wang, J. , Shamah, S. , Sun, A. , Waldman, I. , Haggarty, S. & Perlis, R. (2014) Label‐free, live optical imaging of reprogrammed bipolar disorder patient‐derived cells reveals a functional correlate of lithium responsiveness. Transl. Psychiat., 4, e428.
    1. Wen, Z. , Nguyen, H.N. , Guo, Z. , Lalli, M.A. , Wang, X. , Su, Y. , Kim, N.‐S. , Yoon, K.‐J. et al (2014) Synaptic dysregulation in a human iPS cell model of mental disorders. Nature, 515, 414–418.
    1. Woodard, C.M. , Campos, B.A. , Kuo, S.‐H. , Nirenberg, M.J. , Nestor, M.W. , Zimmer, M. , Mosharov, E.V. , Sulzer, D. et al (2014) iPSC‐derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson's disease. Cell Rep., 9, 1173–1182.
    1. Yoo, J. , Noh, M. , Kim, H. , Jeon, N.L. , Kim, B.‐S. & Kim, J. (2015) Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons. Biomaterials, 45, 36–45.
    1. Yoon, K.‐J. , Nguyen, H.N. , Ursini, G. , Zhang, F. , Kim, N.‐S. , Wen, Z. , Makri, G. , Nauen, D. et al (2014) Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity. Cell Stem Cell, 15, 79–91.
    1. Yu, D.X. , Di Giorgio, F.P. , Yao, J. , Marchetto, M.C. , Brennand, K. , Wright, R. , Mei, A. , Mchenry, L. et al (2014) Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Rep., 2, 295–310.
    1. Zhao, D. , Lin, M. , Chen, J. , Pedrosa, E. , Hrabovsky, A. , Fourcade, H.M. , Zheng, D. & Lachman, H.M. (2015) MicroRNA profiling of neurons generated using induced pluripotent stem cells derived from patients with schizophrenia and schizoaffective disorder, and 22q11. 2 Del. PLoS One, 10, e0132387.

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