リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「In vitro modeling of the bipolar disorder and schizophrenia using patient-derived induced pluripotent stem cells with copy number variations of PCDH15 and RELN (本文)」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

In vitro modeling of the bipolar disorder and schizophrenia using patient-derived induced pluripotent stem cells with copy number variations of PCDH15 and RELN (本文)

石井, 崇也 慶應義塾大学

2021.09.06

概要

Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patient with contributive copy number variations, as follows: two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2 (microtubule-associated protein 2)-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15- or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders.

この論文で使われている画像

参考文献

Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, Morell RJ, Friedman TB, Riazuddin S, Wilcox ER (2001) Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet 69:25–34.

Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, Lowry RB, Knaus R, Van Laer L, Bernier FP, Schwartz S, Lee C, Morton CC, Mullins RF, Ramesh A, Van Camp G, Hageman GS, Woychik RP, Smith RJ (2001) Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Hum Mol Genet 10:10.

Arioka Y, Shishido E, Kubo H, Kushima I, Yoshimi A, Kimura H, Ishizuka K, Aleksic B, Maeda T, Ishikawa M, Kuzumaki N, Okano H, Mori D, Ozaki N (2018) Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant. Transl Psychiatry 8:129.

Bardy C, Van den Hurk M, Eames T, Marchand C, Hernandez RV, Kellogg M, Gorris M, Galet B, Palomares V, Brown J, Bang AG, Mentens J, Bohnke L, Boyer L, Simon S, Gage FH (2015) Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro. Proc Natl Acad SciUSA 112:10.

Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280.

Colasante G, Lignani G, Rubio A, Medrihan L, Yekhlef L, Sessa A, Massimino L, Giannelli SG, Sacchetti S, Caiazzo M, Leo D, Alexopoulou D, Dell’Anno MT, Ciabatti E, Orlando M, Studer M, Dahl A, Gainetdinov RR, Taverna S, Benfenati F, Broccoli V (2015) Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming. Cell Stem Cell 17: 719 –734.

Costain G, Lionel AC, Merico D, Forsythe P, Russell K, Lowther C, Yuen T, Husted J, Stavropoulos DJ, Speevak M, Chow EW, Marshall CR, Scherer SW, Bassett AS (2013) Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays. Hum Mol Genet 22:4485– 4501.

Craddock N, Sklar P (2013) Genetics of bipolar disorder. Lancet 381:1654 –1662.

Espuny-Camacho I, Michelsen KA, Gall D, Linaro D, Hasche A, Bonnefont J, Bali C, Orduz D, Bilheu A, Herpoel A, Lambert N, Gaspard N, Péron S, Schiffmann SN, Giugliano M, Gaillard A, Vanderhaeghen P (2013) Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo. Neuron 77:440 –456.

Flaherty E, Deranieh RM, Artimovich E, Lee IS, Siegel AJ, Levy DL,Nestor MW, Brennand KJ (2017) Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity. NPJ Schizophr 3:35.

Folsom TD, Fatemi SH (2013) The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology 68:122–135.

Fujimori K, Ishikawa M, Otomo A, Atsuta N, Nakamura R, Akiyama T, Hadano S, Aoki M, Saya H, Sobue G, Okano H (2018) Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent. Nat Med 24:1579 –1589.

Gao R, Penzes P (2015) Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders. Curr Mol Med 15:22.

Georgieva L, Rees E, Moran JL, Chambert KD, Milanova V, Craddock N, Purcell S, Sklar P, McCarroll S, Holmans P, O’Donovan MC, Owen MJ, Kirov G (2014) De novo CNVs in bipolar affective disorder and schizophrenia. Hum Mol Genet 23:6677–6683.

Glantz LA, Lewis DA (2000) Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 57:65–73.

Grande I, Berk M, Birmaher B, Vieta E (2016) Bipolar disorder. Lancet 387:1561–1572.

Green EK, Rees E, Walters JT, Smith KG, Forty L, Grozeva D, Moran JL, Sklar P, Ripke S, Chambert KD, Genovese G, McCarroll SA, Jones I, Jones L, Owen MJ, O’Donovan MC, Craddock N, Kirov G (2016) Copy number variation in bipolar disorder. Mol Psychiatry 21:89 –93.

Han SS, Williams LA, Eggan KC (2011) Constructing and deconstructing stem cell models of neurological disease. Neuron 70: 626 –644.

Hino K, Horigome K, Nishio M, Komura S, Nagata S, Zhao C, Jin Y,Kawakami K, Yamada Y, Ohta A, Toguchida J, Ikeya M (2017) Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. J Clin Invest 127: 3339 –3352.

Hirota Y, Nakajima K (2017) Control of neuronal migration and aggregation by reelin signaling in the developing cerebral cortex. Front Cell Dev Biol 5:40.

Hosoya M, Fujioka M, Sone T, Okamoto S, Akamatsu W, Ukai H, Ueda HR, Ogawa K, Matsunaga T, Okano H (2017) Cochlear cell modeling using disease-specific iPSCs unveils a degenerative phenotype and suggests treatments for congenital progressive hearing loss. Cell Rep 18:68 –81.

Imaizumi K, Sone T, Ibata K, Fujimori K, Yuzaki M, Akamatsu W, Okano H (2015) Controlling the regional identity of hpsc-derived neurons to uncover neuronal subtype specificity of neurological disease phenotypes. Stem Cell Reports 5:1010 –1022.

Imaizumi Y, Okada Y, Akamatsu W, Koike M, Kuzumaki N, Hayakawa H, Nihira T, Kobayashi T, Ohyama M, Sato S, Takanashi M, Funayama M, Hirayama A, Soga T, Hishiki T, Suematsu M, Yagi T,

Ito D, Kosakai A, Hayashi K, et al. (2012) Mitochondrial dysfunction associated with increased oxidative stress and -synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue. Mol Brain 5:35.

Imamura K, Izumi Y, Watanabe A, Tsukita K, Woltjen K, Yamamoto T, Hotta A, Kondo T, Kitaoka S, Ohta A, Tanaka A, Watanabe D, Morita M, Takuma H, Tamaoka A, Kunath T, Wray S, Furuya H, Era T, Makioka K, et al. (2017) The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Sci Transl Med 9:eaaf3962.

Ishii K, Kubo KI, Nakajima K (2016) Reelin and neuropsychiatric disorders. Front Cell Neurosci 10:229.

Isoda M, Kohyama J, Iwanami A, Sanosaka T, Sugai K, Yamaguchi R, Matsumoto T, Nakamura M, Okano H (2016) Robust production of human neural cells by establishing neuroepithelial-like stem cells from peripheral blood mononuclear cell-derived feeder-free iPSCs under xeno-free conditions. Neurosci Res 110:18 –28.

Jaiganesh A, Narui Y, Araya-Secchi R, Sotomayor M (2018) Beyond cell-cell adhesion: sensational cadherins for hearing and balance. Cold Spring Harb Perspect Biol 10:a029280.

Kim S-Y, Yasuda S, Tanaka H, Yamagata K, Kim H (2011) Nonclustered protocadherin. Cell Adh Migr 5:97–105.

Kiryushko D, Berezin V, Bock E (2004) Regulators of neurite outgrowth: role of cell adhesion molecules. Ann N Y Acad Sci 1014: 140 –154.

Kondo T, Imamura K, Funayama M, Tsukita K, Miyake M, Ohta A, Woltjen K, Nakagawa M, Asada T, Arai T, Kawakatsu S, Izumi Y,

Kaji R, Iwata N, Inoue H (2017) iPSC-based compound screening and in vitro trials identify a synergistic anti-amyloid combination for Alzheimer’s disease. Cell Rep 21:2304 –2312.

Konopaske GT, Lange N, Coyle JT, Benes FM (2014) Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry 71:1323–1331.

Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, et al. (2017) High-resolution copy number variation analysis of schizophrenia in Japan. Mol Psychiatry 22:430 –440.

Lee GH, D’Arcangelo G (2016) New insights into reelin-mediated signaling pathways. Front Cell Neurosci 10:122.

Lee Y, Zhang Y, Kim S, Han K (2018) Excitatory and inhibitory synaptic dysfunction in mania: an emerging hypothesis from animal model studies. Exp Mol Med 50:12.

Lo MT, Hinds DA, Tung JY, Franz C, Fan CC, Wang Y, Smeland OB, Schork A, Holland D, Kauppi K, Sanyal N, Escott-Price V, Smith DJ, O’Donovan M, Stefansson H, Bjornsdottir G, Thorgeirsson TE, Stefansson K, McEvoy LK, Dale AM, et al. (2017) Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders. Nat Genet 49:152–156.

Madison JM, Zhou F, Nigam A, Hussain A, Barker DD, Nehme R, van der Ven K, Hsu J, Wolf P, Fleishman M, O’Dushlaine C, Rose S, Chambert K, Lau FH, Ahfeldt T, Rueckert EH, Sheridan SD, Fass DM, Nemesh J, Mullen TE, et al. (2015) Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities. Mol Psychiatry 20:703–717.

Maggioni E, Crespo-Facorro B, Nenadic I, Benedetti F, Gaser C, Sauer H, Roiz-Santiañez R, Poletti S, Marinelli V, Bellani M, Perlini C, Ruggeri M, Altamura AC, Diwadkar VA, Brambilla P (2017) Common and distinct structural features of schizophrenia and bipolar disorder: the European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT) study. PLoS One 12:e0188000.

Marin O (2012) Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 13:107–120.

Matsumoto T, Fujimori K, Andoh-Noda T, Ando T, Kuzumaki N, Toyoshima M, Tada H, Imaizumi K, Ishikawa M, Yamaguchi R, Isoda M, Zhou Z, Sato S, Kobayashi T, Ohtaka M, Nishimura K, Kurosawa H, Yoshikawa T, Takahashi T, Nakanishi M, et al. (2016) Functional neurons generated from T cell-derived induced pluripotent stem cells for neurological disease modeling. Stem Cell Reports 6:422–435.

Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK,

Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH (2017) Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun 490:296 –301.

McGrath J, Saha S, Chant D, Welham J (2008) Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 30:67–76.

Millan MJ, Andrieux A, Bartzokis G, Cadenhead K, Dazzan P, FusarPoli P, Gallinat J, Giedd J, Grayson DR, Heinrichs M, Kahn R, Krebs MO, Leboyer M, Lewis D, Marin O, Marin P, MeyerLindenberg A, McGorry P, McGuire P, Owen MJ, et al. (2016) Altering the course of schizophrenia: progress and perspectives.

Nat Rev Drug Discov 15:485–515. Missler M, Südhof TC, Biederer T (2012) Synaptic cell adhesion. Cold Spring Harb Perspect Biol 4:a005694.

Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K, Morizane A, Doi D, Takahashi J, Nishizawa M, Yoshida Y, Toyoda T, Osafune K, Sekiguchi K, Yamanaka S (2014) A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. Sci Rep 4:3594.

Nehme R, Zuccaro E, Ghosh SD, Li C, Sherwood JL, Pietilainen O, Barrett LE, Limone F, Worringer KA, Kommineni S, Zang Y, Cacchiarelli D, Meissner A, Adolfsson R, Haggarty S, Madison J, Muller M, Arlotta P, Fu Z, Feng G, et al. (2018) Combining NGN2 programming with developmental patterning generates human excitatory neurons with NMDAR-mediated synaptic transmission. Cell Rep 23:2509 –2523.

Noor A, Lionel AC, Cohen-Woods S, Moghimi N, Rucker J, Fennell A, Thiruvahindrapuram B, Kaufman L, Degagne B, Wei J, Parikh SV, Muglia P, Forte J, Scherer SW, Kennedy JL, Xu W, McGuffin P, Farmer A, Strauss J, Vincent JB (2014) Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes. Am J Med Genet B Neuropsychiatr Genet 165B: 303–313.

O’Dushlaine C, Kenny E, Heron E, Donohoe G, Gill M, Morris D, Corvin A (2011) Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility. Mol Psychiatry 16:286 –292.

Okada Y, Shimazaki T, Sobue G, Okano H (2004) Retinoic-acidconcentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells. Dev Biol 275:124 –142.

Okano H, Yamanaka S (2014) iPS cell technologies: significance and applications to CNS regeneration and disease. Mol Brain 7:22.

Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Methods 8:409 –412.

Okita K, Yamakawa T, Matsumura Y, Sato Y, Amano N, Watanabe A, Goshima N, Yamanaka S (2013) An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells 31:458 – 466.

O’Shea KS, McInnis MG (2016) Neurodevelopmental origins of bipolar disorder: iPSC models. Mol Cell Neurosci 73:63–83.

Owen MJ, O’Donovan MC (2017) Schizophrenia and the neurodevelopmental continuum: evidence from genomics. World Psychiatry 16:227–235.

Prytkova I, Brennand KJ (2017) Prospects for modeling abnormal neuronal function in schizophrenia using human induced pluripotent stem cells. Front Cell Neurosci 11:360. Rutkowski TP, Schroeder JP, Gafford GM, Warren ST, Weinshenker D, Caspary T, Mulle JG (2017) Unraveling the genetic architecture of copy number variants associated with schizophrenia and other neuropsychiatric disorders. J Neurosci Res 95:1144 –1160.

Sakurai T (2017) The role of cell adhesion molecules in brain wiring and neuropsychiatric disorders. Mol Cell Neurosci 81:4 –11.

Sekine K, Kawauchi T, Kubo K, Honda T, Herz J, Hattori M, Kinashi T, Nakajima K (2012) Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin 51. Neuron 76:353–369.

Shimazaki T, Shingo T, Weiss S (2001) The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. J Neurosci 21:7642–7653.

Sobue A, Kushima I, Nagai T, Shan W, Kohno T, Aleksic B, Aoyama Y, Mori D, Arioka Y, Kawano N, Yamamoto M, Hattori M, Nabeshima T, Yamada K, Ozaki N (2018) Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia. Sci Rep 8:13046.

Sun AX, Yuan Q, Tan S, Xiao Y, Wang D, Khoo AT, Sani L, Tran HD, Kim P, Chiew YS, Lee KJ, Yen YC, Ng HH, Lim B, Je HS (2016) Direct induction and functional maturation of forebrain GABAergic neurons from human pluripotent stem cells. Cell Rep 16:1942– 1953.

Tabata Y, Imaizumi Y, Sugawara M, Ando-Noda T, Banno S, Chai M, Sone T, Yamazaki K, Ito M, Tsukahara K, Saya H, Hattori N, Kohyama J, Okano H (2018) T-type calcium channels determine the vulnerability of dopaminergic neurons to mitochondrial stress in familial Parkinson’s disease. Stem Cell Reports 11:1171–1184.

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.

Tobe BTD, Crain AM, Winquist AM, Calabrese B, Snyder EY (2017) Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis. Proc Natl Acad SciUSA 114:10.

Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, Iwayama Y, Toyota T, Matsumoto T, Itasaka N, Sugiyama S,

Tanaka M, Yano M, Dean B, Okano H, Yoshikawa T (2016) Analysis of induced pluripotent stem cells carrying 22q11.2 deletion. Transl Psychiatry 6:e934.

Wainger BJ, Kiskinis E, Mellin C, Wiskow O, Han SS, Sandoe J, Perez NP, Williams LA, Lee S, Boulting G, Berry JD, Brown RH Jr, Cudkowicz ME, Bean BP, Eggan K, Woolf CJ (2014) Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep 7:1–11.

Wang AY, Lohmann KM, Yang CK, Zimmerman EI, Pantazopoulos H, Herring N, Berretta S, Heckers S, Konradi C (2011) Bipolar disorder type 1 and schizophrenia are accompanied by decreased density of parvalbumin- and somatostatin-positive interneurons in the parahippocampal region. Acta Neuropathol 122:615–626.

Watmuff B, Berkovitch SS, Huang JH, Iaconelli J, Toffel S, Karmacharya R (2016) Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells. Mol Cell Neurosci 73:96 –103.

Wen Z (2017) Modeling neurodevelopmental and psychiatric diseases with human iPSCs. J Neurosci Res 95:1097–1109.

Yang N, Chanda S, Marro S, Ng YH, Janas JA, Haag D, Ang CE, Tang Y, Flores Q, Mall M, Wapinski O, Li M, Ahlenius H, Rubenstein JL, Chang HY, Buylla AA, Südhof TC, Wernig M (2017) Generation of pure GABAergic neurons by transcription factor programming. Nat Methods 14:621–628.

Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Südhof TC (2013) Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78:785–798.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る