Modeling schizophrenia pathogenesis using patient-derived induced pluripotent stem cells (iPSCs)

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1863, Issue 9, 2017, Pages 2382-2387

  Noh, Haneul ^a   Shao, Zhicheng ^a   Coyle, Joseph T ^a   Chung, Sangmi ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Differentiation; iPSC; Neural progenitor cell; Schizophrenia

Indexed keywords

CELL DISRUPTION; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; INDUCED PLURIPOTENT STEM CELL; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; TISSUES; ANIMAL; BIOLOGICAL MODEL; METABOLISM; PATHOLOGY;

ANIMALS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MODELS, BIOLOGICAL; SCHIZOPHRENIA;

EID: 85022031893     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2017.06.019     Document Type: Review

References (79)

1. Sullivan, P.F., Kendler, K.S., Neale, M.C., Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60 (2003), 1187–1192, 10.1001/archpsyc.60.12.1187.
2. Weinberger, D.R., Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44 (1987), 660–669.
3. Carpenter, W.T., Buchanan, R.W., Schizophrenia. N. Engl. J. Med. 330 (1994), 681–690, 10.1056/NEJM199403103301006.
4. Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z., Keith, S.J., Judd, L.L., Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 264 (1990), 2511–2518.
5. Radomsky, E.D., Haas, G.L., Mann, J.J., Sweeney, J.A., Suicidal behavior in patients with schizophrenia and other psychotic disorders. Am. J. Psychiatry 156 (1999), 1590–1595, 10.1176/ajp.156.10.1590.
6. Lewis, D.A., Lieberman, J.A., Catching up on schizophrenia: natural history and neurobiology. Neuron 28 (2000), 325–334.
7. Elvevåg, B., Goldberg, T.E., Cognitive impairment in schizophrenia is the core of the disorder. Crit. Rev. Neurobiol. 14 (2000), 1–21.
8. Bellack, A.S., Scientific and consumer models of recovery in schizophrenia: concordance, contrasts, and implications. Schizophr. Bull. 32 (2006), 432–442, 10.1093/schbul/sbj044.
9. Stachowiak, M.K., Kucinski, A., Curl, R., Syposs, C., Yang, Y., Narla, S., Terranova, C., Prokop, D., Klejbor, I., Bencherif, M., Birkaya, B., Corso, T., Parikh, A., Tzanakakis, E.S., Wersinger, S., Stachowiak, E.K., Schizophrenia: a neurodevelopmental disorder–integrative genomic hypothesis and therapeutic implications from a transgenic mouse model. Schizophr. Res. 143 (2013), 367–376, 10.1016/j.schres.2012.11.004.
10. Jones, C.A., Watson, D.J.G., Fone, K.C.F., Animal models of schizophrenia. Br. J. Pharmacol. 164 (2011), 1162–1194, 10.1111/j.1476-5381.2011.01386.x.
11. Thomsen, M.S., Hansen, H.H., Timmerman, D.B., Mikkelsen, J.D., Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr. Pharm. Des. 16 (2010), 323–343.
12. Franco, R., Cedazo-Minguez, A., Successful therapies for Alzheimer's disease: why so many in animal models and none in humans?. Front. Pharmacol., 5, 2014, 146, 10.3389/fphar.2014.00146.
13. Rajkowska, G., Selemon, L.D., Goldman-Rakic, P.S., Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch. Gen. Psychiatry 55 (1998), 215–224.
14. Black, J.E., Kodish, I.M., Grossman, A.W., Klintsova, A.Y., Orlovskaya, D., Vostrikov, V., Pathology of layer V pyramidal neurons in the prefrontal cortex of patients with schizophrenia. Am. J. Psychiatry 161 (2004), 742–744, 10.1176/appi.ajp.161.4.742.
15. Garey, L.J., Ong, W.Y., Patel, T.S., Kanani, M., Davis, A., Mortimer, A.M., Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J. Neurol. Neurosurg. Psychiatry 65 (1998), 446–453.
16. Kalus, P., Bondzio, J., Federspiel, A., Müller, T.J., Zuschratter, W., Cell-type specific alterations of cortical interneurons in schizophrenic patients. Neuroreport 13 (2002), 713–717.
17. Guidotti, A., Auta, J., Davis, J.M., Di-Giorgi-Gerevini, V., Dwivedi, Y., Grayson, D.R. et al., Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch. Gen. Psychiatry 57 (2000), 1061–1069.
18. Volk, D., Austin, M., Pierri, J., Sampson, A., Lewis, D., GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons. Am. J. Psychiatry 158 (2001), 256–265, 10.1176/appi.ajp.158.2.256.
19. Reynolds, G.P., Abdul-Monim, Z., Neill, J.C., Zhang, Z.-J., Calcium binding protein markers of GABA deficits in schizophrenia–postmortem studies and animal models. Neurotox. Res. 6 (2004), 57–61.
20. Hashimoto, T., Volk, D.W., Eggan, S.M., Mirnics, K., Pierri, J.N., Sun, Z., Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J. Neurosci. 23 (2003), 6315–6326.
21. Meyer-Lindenberg, A., From maps to mechanisms through neuroimaging of schizophrenia. Nature 468 (2010), 194–202, 10.1038/nature09569.
22. Bogerts, B., Häntsch, J., Herzer, M., A morphometric study of the dopamine-containing cell groups in the mesencephalon of normals, Parkinson patients, and schizophrenics. Biol. Psychiatry 18 (1983), 951–969.
23. Ikemoto, K., Striatal D-neurons: in new viewpoints for neuropsychiatric research using post-mortem brains. Fukushima J. Med. Sci. 54 (2008), 1–3.
24. Laruelle, M., Imaging dopamine transmission in schizophrenia. A review and meta-analysis. Q. J. Nucl. Med. 42 (1998), 211–221.
25. Millan, M.J., Andrieux, A., Bartzokis, G., Cadenhead, K., Dazzan, P., Fusar-Poli, P., Altering the course of schizophrenia: progress and perspectives. Nat. Rev. Drug Discov. 15 (2016), 485–515, 10.1038/nrd.2016.28.
26. Gilman, S.R., Chang, J., Xu, B., Bawa, T.S., Gogos, J.A., Karayiorgou, M., Diverse types of genetic variation converge on functional gene networks involved in schizophrenia. Nature 15 (2012), 1723–1728, 10.1038/nn.3261.
27. Xu, B., Ionita-Laza, I., Roos, J.L., Boone, B., Woodrick, S., Sun, Y., De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat. Genet. 44 (2012), 1365–1369.
28. Lin, M., Pedrosa, E., Shah, A., Hrabovsky, A., Maqbool, S., Zheng, D., RNA-seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS One, 6, 2011, e23356.
29. Belforte, J.E., Zsiros, V., Sklar, E.R., Jiang, Z., Yu, G., Li, Y., Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat. Neurosci. 13 (2010), 76–83, 10.1038/nn.2447.
30. Aguilar-Valles, A., Luheshi, G.N., Alterations in cognitive function and behavioral response to amphetamine induced by prenatal inflammation are dependent on the stage of pregnancy. Psychoneuroendocrinology 36 (2011), 634–648.
31. Li, Q., Cheung, C., Wei, R., Hui, E.S., Feldon, J., Meyer, U., Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model. PLoS One, 4, 2009, e6354.
32. Piper, M., Beneyto, M., Burne, T.H., Eyles, D.W., Lewis, D.A., McGrath, J.J., The neurodevelopmental hypothesis of schizophrenia: convergent clues from epidemiology and neuropathology. Psychiatr. Clin. North Am. 35 (2012), 571–584, 10.1016/j.psc.2012.06.002.
33. Takahashi, K., Yamanaka, S., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (2006), 663–676, 10.1016/j.cell.2006.07.024.
34. Nicholas, C.R., Chen, J., Tang, Y., Southwell, D.G., Chalmers, N., Vogt, D., Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12 (2013), 573–586, 10.1016/j.stem.2013.04.005.
35. Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78 (2013), 785–798, 10.1016/j.neuron.2013.05.029.
36. Mertens, J., Paquola, A.C.M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 17 (2015), 705–718, 10.1016/j.stem.2015.09.001.
37. Wainger, B.J., Kiskinis, E., Mellin, C., Wiskow, O., Han, S.S.W., Sandoe, J., Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 7 (2014), 1–11, 10.1016/j.celrep.2014.03.019.
38. Lin, M., Pedrosa, E., Hrabovsky, A., Chen, J., Puliafito, B.R., Gilbert, S.R., Integrative transcriptome network analysis of iPSC-derived neurons from schizophrenia and schizoaffective disorder patients with 22q11.2 deletion. BMC Syst. Biol., 10, 2016, 105, 10.1186/s12918-016-0366-0.
39. Toyoshima, M., Akamatsu, W., Okada, Y., Ohnishi, T., Balan, S., Hisano, Y., Analysis of induced pluripotent stem cells carrying 22q11.2 deletion. Transl. Psychiatry, 6, 2016, e934, 10.1038/tp.2016.206.
40. Zhao, D., Lin, M., Chen, J., Pedrosa, E., Hrabovsky, A., Fourcade, H.M., 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, 2015, e0132387-24, 10.1371/journal.pone.0132387.
41. Yoon, K.-J., Nguyen, H.N., Ursini, G., Zhang, F., Kim, N.-S., Wen, Z., Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity. Stem Cells 15 (2014), 79–91, 10.1016/j.stem.2014.05.003.
42. Lee, I.S., Carvalho, C.M.B., Douvaras, P., Ho, S.-M., Hartley, B.J., Zuccherato, L.W., Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells. NPJ Schizophr. 1 (2015), 15019–15025, 10.1038/npjschz.2015.19.
43. Srikanth, P., Han, K., Callahan, D.G., Makovkina, E., Muratore, C.R., Lalli, M.A., Genomic DISC1 disruption in hiPSCs alters Wnt signaling and neural cell fate. Cell Rep. 12 (2015), 1414–1429, 10.1016/j.celrep.2015.07.061.
44. Wen, Z., Nguyen, H.N., Guo, Z., Lalli, M.A., Wang, X., Su, Y., Kim, N.S., Yoon, K.J., Shin, J., Zhang, C., Makri, G., Nauen, D., Yu, H., Guzman, E., Chiang, C.H., Yoritomo, N., Kaibuchi, K., Zou, J., Christian, K.M., Cheng, L., Ross, C.A., Margolis, R.L., Chen, G., Kosik, K.S., Song, H., Ming, G.L., Synaptic dysregulation in a human iPS cell model of mental disorders. Nature, 2014, 1–15.
45. Topol, A., English, J.A., Flaherty, E., Rajarajan, P., Hartley, B.J., Gupta, S., Increased abundance of translation machinery in stem cell-derived neural progenitor cells from four schizophrenia patients. Transl. Psychiatry, 5, 2015, e662.
46. Brennand, K., Savas, J.N., Kim, Y., Tran, N., Simone, A., Hashimoto-Torii, K., Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatry 20 (2015), 361–368, 10.1038/mp.2014.22.
47. Roussos, P., Guennewig, B., Kaczorowski, D.C., Barry, G., Brennand, K.J., Activity-dependent changes in gene expression in schizophrenia human-induced pluripotent stem cell neurons. JAMA Psychiatry 73 (2016), 1180–1188, 10.1001/jamapsychiatry.2016.2575.
48. Narla, S.T., Lee, Y.-W., Benson, C.A., Sarder, P., Brennand, K.J., Stachowiak, E.K., Common developmental genome deprogramming in schizophrenia - role of integrative nuclear FGFR1 signaling (INFS). Schizophr. Res., 2017, 10.1016/j.schres.2016.12.012.
49. Topol, A., Zhu, S., Hartley, B.J., English, J., Hauberg, M.E., Tran, N., Dysregulation of miRNA-9 in a subset of schizophrenia patient-derived neural progenitor cells. Cell Rep. 15 (2016), 1024–1036, 10.1016/j.celrep.2016.03.090.
50. Ripke, S., Neale, B.M., Corvin, A., Walters, J.T.R., Farh, K.-H., Holmans, P.A., Biological insights from 108 schizophrenia-associated genetic loci. Nature 511 (2014), 421–427, 10.1038/nature13595.
51. Chatterjee, N., Wheeler, B., Sampson, J., Hartge, P., Chanock, S.J., Park, J.-H., Projecting the performance of risk prediction based on polygenic analyses of genome-wide association studies. Nat. Genet., 45, 2013, 10.1038/ng.2579 (400–5–405e1–3).
52. Topol, A., Zhu, S., Tran, N., Simone, A., Fang, G., Brennand, K.J., Altered WNT signaling in human induced pluripotent stem cell neural progenitor cells derived from four schizophrenia patients. Biol. Psychiatry 78 (2015), e29–e34, 10.1016/j.biopsych.2014.12.028.
53. Hartley, B.J., Tran, N., Ladran, I., Reggio, K., Brennand, K.J., Dopaminergic differentiation of schizophrenia hiPSCs. Mol. Psychiatry 20 (2015), 549–550, 10.1038/mp.2014.194.
54. Ahn, S., Kim, T.-G., Kim, K.-S., Chung, S., Differentiation of human pluripotent stem cells into medial ganglionic eminence vs. caudal ganglionic eminence cells. Methods 101 (2016), 103–112, 10.1016/j.ymeth.2015.09.009.
55. Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78 (2013), 785–798, 10.1016/j.neuron.2013.05.029.
56. Kim, T.-G., Yao, R., Monnell, T., Cho, J.-H., Vasudevan, A., Koh, A., Efficient specification of interneurons from human pluripotent stem cells by dorsoventral and rostrocaudal modulation. Stem Cells 32 (2014), 1789–1804, 10.1002/stem.1704.
57. Lewis, D.A., Hashimoto, T., Volk, D.W., Cortical inhibitory neurons and schizophrenia. Nat. Rev. Neurosci. 6 (2005), 312–324.
58. Volk, D.W., Lewis, D.A., Early developmental disturbances of cortical inhibitory neurons: contribution to cognitive deficits in schizophrenia. Schizophr. Bull. 40 (2014), 952–957, 10.1093/schbul/sbu111.
59. Lewis, D.A., Cho, R.Y., Carter, C.S., Eklund, K., Forster, S., Kelly, M.A., Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am. J. Psychiatry 165 (2008), 1585–1593.
60. Enomoto, T., Tse, M.T., Floresco, S.B., Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia. Biol. Psychiatry 69 (2011), 432–441.
61. Howes, O.D., Kapur, S., The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr. Bull. 35 (2009), 549–562, 10.1093/schbul/sbp006.
62. Hook, V., Brennand, K.J., Kim, Y., Toneff, T., Funkelstein, L., Lee, K.C., Human iPSC neurons display activity-dependent neurotransmitter secretion: aberrant catecholamine levels in schizophrenia neurons. Stem Cell Rep. 3 (2014), 531–538, 10.1016/j.stemcr.2014.08.001.
63. Robicsek, O., Karry, R., Petit, I., Salman-Kesner, N., Ller, F.-J.M.U., Klein, E., Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients. Mol. Psychiatry 18 (2013), 1067–1076, 10.1038/mp.2013.67.
64. Arenas, E., Denham, M., Villaescusa, J.C., How to make a midbrain dopaminergic neuron. Development 142 (2015), 1918–1936, 10.1242/dev.097394.
65. Chung, S., Moon, J.-I., Leung, A., Aldrich, D., Lukianov, S., Kitayama, Y., ES cell-derived renewable and functional midbrain dopaminergic progenitors. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 9703–9708, 10.1073/pnas.1016443108.
66. Bernstein, H.-G., Steiner, J., Guest, P.C., Dobrowolny, H., Bogerts, B., Glial cells as key players in schizophrenia pathology: recent insights and concepts of therapy. Schizophr. Res. 161 (2015), 4–18, 10.1016/j.schres.2014.03.035.
67. Krencik, R., Weick, J.P., Liu, Y., Zhang, Z.-J., Zhang, S.-C., Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat. Biotechnol. 29 (2011), 528–534, 10.1038/nbt.1877.
68. Hu, B.-Y., Du, Z.-W., Li, X.-J., Ayala, M., Zhang, S.-C., Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136 (2009), 1443–1452, 10.1242/dev.029447.
69. Lancaster, M.A., Renner, M., Martin, C.A., Wenzel, D., Bicknell, L.S., Hurles, M.E., Homfray, T., Penninger, J.M., Jackson, A.P., Knoblich, J.A., Cerebral organoids model human brain development and microcephaly. Nature 501 (2014), 373–379.
70. Moreau, Y., Tranchevent, L.C., Computational tools for prioritizing candidate genes: boosting disease gene discovery. Nat. Rev. Genet. 13 (2012), 523–536.
71. Fromer, M., Roussos, P., Sieberts, S.K., Johnson, J.S., Kavanagh, D.H., Perumal, T.M., Gene expression elucidates functional impact of polygenic risk for schizophrenia. Nat. Neurosci., 2016, 10.1038/nn.4399.
72. Warren, C.R., Jaquish, C.E., Cowan, C.A., The NextGen genetic association studies consortium: a foray into in vitro population genetics. Cell Stem Cell 20 (2017), 431–433, 10.1016/j.stem.2017.03.021.
73. Warren, C.R., O'Sullivan, J.F., Friesen, M., Becker, C.E., Zhang, X., Liu, P., Induced pluripotent stem cell differentiation enables functional validation of GWAS variants in metabolic disease. Cell Stem Cell, 20, 2017, 10.1016/j.stem.2017.01.010 (547-557.e7).
74. van Os, J., Kenis, G., Rutten, B.P., The environment and schizophrenia. Nature 468 (2010), 203–212.
75. Brown, A.S., Progress in neurobiology. Prog. Neurobiol. 93 (2011), 23–58, 10.1016/j.pneurobio.2010.09.003.
76. Rouhani, F., Kumasaka, N., de Brito, M.C., Bradley, A., Vallier, L., Gaffney, D., Genetic background drives transcriptional variation in human induced pluripotent stem cells. PLoS Genet., 10, 2014, e1004432, 10.1371/journal.pgen.1004432.
77. Choi, J., Lee, S., Mallard, W., Clement, K., Tagliazucchi, G.M., Lim, H., A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs. Nat. Biotechnol. 33 (2015), 1173–1181, 10.1038/nbt.3388.
78. Warren, L., Manos, P.D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7 (2010), 618–630, 10.1016/j.stem.2010.08.012.
79. Birey, F., Andersen, J., Makinson, C.D., Islam, S., Wei, W., Huber, N., Assembly of functionally integrated human forebrain spheroids. Nature 545 (2017), 54–59, 10.1038/nature22330.