Modeling neuropsychiatric disorders using human induced pluripotent stem cells
Received date: 22 Mar 2019
Accepted date: 03 May 2019
Published date: 15 Jan 2020
Copyright
Neuropsychiatric disorders are complex disorders characterized by heterogeneous genetic variations, variable symptoms, and widespread changes in anatomical pathology. In the context of neuropsychiatric disorders, limited access to relevant tissue types presents challenges for understanding disease etiology and developing effective treatments. Induced pluripotent stem cells (iPSCs) reprogrammed from patient somatic cells offer an opportunity to recapitulate disease development in relevant cell types, and they provide novel approaches for understanding disease mechanisms and for development of effective treatments. Here we review recent progress and challenges in differentiation paradigms for generating disease-relevant cells and recent studies of neuropsychiatric disorders using human pluripotent stem cell (hPSC) models where cellular phenotypes linked to disease have been reported. The use of iPSC-based disease models holds great promise for understanding disease mechanisms and supporting discovery of effective treatments.
Meiyan Wang , Lei Zhang , Fred H. Gage . Modeling neuropsychiatric disorders using human induced pluripotent stem cells[J]. Protein & Cell, 2020 , 11(1) : 45 -59 . DOI: 10.1007/s13238-019-0638-8
1 |
Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, Yeromin AV, Scarfone VM, Marsh SE, Fimbres C
|
2 |
Amiri A, Coppola G, Scuderi S, Wu F, Roychowdhury T, Liu F, Pochareddy S, Shin Y, Safi A, Song L
|
3 |
Bagley JA, Reumann D, Bian S, Levi-Strauss J, Knoblich JA (2017) Fused cerebral organoids model interactions between brain regions. Nat Methods 14:743–751
|
4 |
Bavamian S, Mellios N, Lalonde J, Fass DM, Wang J, Sheridan SD, Madison JM, Zhou F, Rueckert EH, Barker D
|
5 |
Bershteyn M, Nowakowski TJ, Pollen AA, Di Lullo E, Nene A, Wynshaw-Boris A, Kriegstein AR (2017) Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia. Cell Stem Cell 20 (435–449):e434
|
6 |
Bipolar D, Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address, d.r.v.e., Bipolar, D., and Schizophrenia Working Group of the PsychiatricGenomics, C (2018) Genomic dissection of bipolar disorder and schizophrenia, including 28 SUBPHENOTYPES. Cell 173:1705e1716–1715e1716
|
7 |
Birey F, Andersen J, Makinson CD, Islam S, Wei W, Huber N, Fan HC, Metzler KRC, Panagiotakos G, Thom N
|
8 |
Brennand K, Savas JN, Kim Y, Tran N, Simone A, Hashimoto-Torii K, Beaumont KG, Kim HJ, Topol A, Ladran I
|
9 |
Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D
|
10 |
Bundo M, Toyoshima M, Okada Y, Akamatsu W, Ueda J, Nemoto-Miyauchi T, Sunaga F, Toritsuka M, Ikawa D, Kakita A
|
11 |
Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE
|
12 |
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
|
13 |
Ciani L, Salinas PC (2005) WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 6:351–362
|
14 |
Cirillo MA, Seidman LJ (2003) Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychol Rev 13:43–77
|
15 |
Darmanis S, Sloan SA, Zhang Y, Enge M, Caneda C, Shuer LM, Hayden Gephart MG, Barres BA, Quake SR (2015) A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci U S A 112:7285–7290
|
16 |
Dehay C, Kennedy H, Kosik KS (2015) The outer subventricular zone and primate-specific cortical complexification. Neuron 85:683–694
|
17 |
Deshpande A, Yadav S, Dao DQ, Wu ZY, Hokanson KC, Cahill MK, Wiita AP, Jan YN, Ullian EM, Weiss LA (2017) Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder. Cell Rep 21:2678–2687
|
18 |
Di Lullo E, Kriegstein AR (2017) The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci 18:573–584
|
19 |
Edlund T, Jessell TM (1999) Progression from extrinsic to intrinsic signalling in cell fate specification: a view from the nervous system. Cell 96:211–224
|
20 |
Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S, Matsumura M, Wataya T, Nishiyama A, Muguruma K, Sasai Y (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3:519–532
|
21 |
Emery B (2010) Regulation of oligodendrocyte differentiation and myelination. Science 330:779–782
|
22 |
Espuny-Camacho I, Michelsen KA, Gall D, Linaro D, Hasche A, Bonnefont J, Bali C, Orduz D, Bilheu A, Herpoel A
|
23 |
Feinberg I (1982) Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res 17:319–334
|
24 |
Freedman R, Goldowitz D (2010) Studies on the hippocampal formation: From basic development to clinical applications: Studies on schizophrenia. Prog Neurobiol 90:263–275
|
25 |
Fuccillo M, Joyner AL, Fishell G (2006) Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci 7:772–783
|
26 |
Galceran J, Miyashita-Lin EM, Devaney E, Rubenstein JL, Grosschedl R (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development 127:469–482
|
27 |
Gaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, van den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Schiffmann SN
|
28 |
Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER
|
29 |
Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E
|
30 |
Greter M, Lelios I, Pelczar P, Hoeffel G, Price J, Leboeuf M, Kundig TM, Frei K, Ginhoux F, Merad M
|
31 |
Griesi-Oliveira K, Acab A, Gupta AR, Sunaga DY, Chailangkarn T, Nicol X, Nunez Y, Walker MF, Murdoch JD, Sanders SJ
|
32 |
Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R
|
33 |
Guillemot F, Zimmer C (2011) From cradle to grave: the multiple roles of fibroblast growth factors in neural development. Neuron 71:574–588
|
34 |
Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A 98:4746–4751
|
35 |
Hashimoto-Torii K, Torii M, Fujimoto M, Nakai A, El Fatimy R, Mezger V, Ju MJ, Ishii S, Chao SH, Brennand KJ
|
36 |
Hook V, Brennand KJ, Kim Y, Toneff T, Funkelstein L, Lee KC, Ziegler M, Gage FH (2014) Human iPSC neurons display activitydependent neurotransmitter secretion: aberrant catecholamine levels in schizophrenia neurons. Stem Cell Rep 3:531–538
|
37 |
Hu BY, Du ZW, Zhang SC (2009) Differentiation of human oligodendrocytes from pluripotent stem cells. Nat Protoc 4:1614–1622
|
38 |
Iefremova V, Manikakis G, Krefft O, Jabali A, Weynans K, Wilkens R, Marsoner F, Brandl B, Muller FJ, Koch P
|
39 |
Ji J, Ng SH, Sharma V, Neculai D, Hussein S, Sam M, Trinh Q, Church GM, McPherson JD, Nagy A
|
40 |
Jo J, Xiao Y, Sun AX, Cukuroglu E, Tran HD, Goke J, Tan ZY, Saw TY, Tan CP, Lokman H
|
41 |
Jones JR, Kong L, Hanna MGT, Hoffman B, Krencik R, Bradley R, Hagemann T, Choi J, Doers M, Dubovis M
|
42 |
Kadoshima T, Sakaguchi H, Nakano T, Soen M, Ando S, Eiraku M, Sasai Y (2013) Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A 110:20284–20289
|
43 |
Kang E, Wang X, Tippner-Hedges R, Ma H, Folmes CD, Gutierrez NM, Lee Y, Van Dyken C, Ahmed R, Li Y
|
44 |
Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705
|
45 |
Kelsom C, Lu W (2013) Development and specification of GABAergic cortical interneurons. Cell Biosci 3:19
|
46 |
Kepecs A, Fishell G (2014) Interneuron cell types are fit to function. Nature 505:318–326
|
47 |
Kerr CL, Letzen BS, Hill CM, Agrawal G, Thakor NV, Sterneckert JL, Gearhart JD, All AH (2010) Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury. Int J Neurosci 120:305–313
|
48 |
Khakh BS, Sofroniew MV (2015) Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci 18:942–952
|
49 |
Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, Wieghofer P, Heinrich A, Riemke P, Holscher C
|
50 |
Kolomeets NS, Orlovskaya DD, Uranova NA (2007) Decreased numerical density of CA3 hippocampal mossy fiber synapses in schizophrenia. Synapse 61:615–621
|
51 |
Krencik R, Weick JP, Liu Y, Zhang ZJ, Zhang SC (2011) Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat Biotechnol 29:528–534
|
52 |
Krencik R, Zhang SC (2011) Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc 6:1710–1717
|
53 |
Lake BB, Ai R, Kaeser GE, Salathia NS, Yung YC, Liu R, Wildberg A, Gao D, Fung HL, Chen S
|
54 |
Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature 501:373–379
|
55 |
Lee S, Hjerling-Leffler J, Zagha E, Fishell G, Rudy B (2010) The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. J Neurosci 30:16796–16808
|
56 |
Lee SM, Tole S, Grove E, McMahon AP (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127:457–467
|
57 |
Li L, Tian E, Chen X, Chao J, Klein J, Qu Q, Sun G, Sun G, Huang Y, Warden CD
|
58 |
Li W, Ghose S, Gleason K, Begovic A, Perez J, Bartko J, Russo S, Wagner AD, Selemon L, Tamminga CA (2015) Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia. Am J Psychiatry 172:373–382
|
59 |
Li Y, Muffat J, Omer A, Bosch I, Lancaster MA, Sur M, Gehrke L, Knoblich JA, Jaenisch R (2017) Induction of expansion and folding in human cerebral organoids. Cell Stem Cell 20(385–396): e383
|
60 |
Liu A, Niswander LA (2005) Bone morphogenetic protein signalling and vertebrate nervous system development. Nat Rev Neurosci 6:945–954
|
61 |
Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC (2013) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc 8:1670–1679
|
62 |
Maden M (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8:755–765
|
63 |
Madhavan M, Nevin ZS, Shick HE, Garrison E, Clarkson-Paredes C, Karl M, Clayton BLL, Factor DC, Allan KC, Barbar L
|
64 |
Madison JM, Zhou F, Nigam A, Hussain A, Barker DD, Nehme R, van der Ven K, Hsu J, Wolf P, Fleishman M
|
65 |
Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, Johnston S, Parylak SL, Jin X, Gage FH (2018) An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36:432–441
|
66 |
Marchetto MC, Belinson H, Tian Y, Freitas BC, Fu C, Vadodaria K, Beltrao-Braga P, Trujillo CA, Mendes APD, Padmanabhan K
|
67 |
Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–539
|
68 |
Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, Amenduni M, Szekely A, Palejev D, Wilson M
|
69 |
Maroof AM, Keros S, Tyson JA, Ying SW, Ganat YM, Merkle FT, Liu B, Goulburn A, Stanley EG, Elefanty AG
|
70 |
Mayer C, Hafemeister C, Bandler RC, Machold R, Batista Brito R, Jaglin X, Allaway K, Butler A, Fishell G, Satija R (2018) Developmental diversification of cortical inhibitory interneurons. Nature 555:457–462
|
71 |
Mertens J, Marchetto MC, Bardy C, Gage FH (2016) Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat Rev Neurosci 17:424–437
|
72 |
Mertens J, Wang QW, Kim Y, Yu DX, Pham S, Yang B, Zheng Y, Diffenderfer KE, Zhang J, Soltani S
|
73 |
Miller FD, Gauthier AS (2007) Timing is everything: making neurons versus glia in the developing cortex. Neuron 54:357–369
|
74 |
Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa VH, Butt SJ, Battiste J, Johnson JE, Machold RP, Fishell G (2010) Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J Neurosci 30:1582–1594
|
75 |
Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ (2000) Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101:499–510
|
76 |
Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM
|
77 |
Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y (2015) Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep 10:537–550
|
78 |
Munoz-Sanjuan I, Brivanlou AH (2002) Neural induction, the default model and embryonic stem cells. Nat Rev Neurosci 3:271–280
|
79 |
Murai K, Sun G, Ye P, Tian E, Yang S, Cui Q, Sun G, Trinh D, Sun O, Hong T
|
80 |
Nave KA, Ehrenreich H (2014) Myelination and oligodendrocyte functions in psychiatric diseases. JAMA Psychiatry 71:582–584
|
81 |
Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–1169
|
82 |
Nicholas CR, Chen J, Tang Y, Southwell DG, Chalmers N, Vogt D, Arnold CM, Chen YJ, Stanley EG, Elefanty AG
|
83 |
Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS (2005) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396
|
84 |
Pandya H, Shen MJ, Ichikawa DM, Sedlock AB, Choi Y, Johnson KR, Kim G, Brown MA, Elkahloun AG, Maric D
|
85 |
Pasca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, Kim CH, Park JY, O’Rourke NA, Nguyen KD
|
86 |
Pasca SP (2018) The rise of three-dimensional human brain cultures. Nature 553:437–445
|
87 |
Pasca SP (2019) Assembling human brain organoids. Science 363:126–127
|
88 |
Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A, Pasca AM, Cord B, Palmer TD, Chikahisa S, Nishino S
|
89 |
Piao J, Major T, Auyeung G, Policarpio E, Menon J, Droms L, Gutin P, Uryu K, Tchieu J, Soulet D
|
90 |
Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, Yao B, Hamersky GR, Jacob F, Zhong C
|
91 |
Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Min Yang S, Berger DR, Maria N, Scholvin J, Goldman M, Kinney JP
|
92 |
Rasetti R, Mattay VS, White MG, Sambataro F, Podell JE, Zoltick B, Chen Q, Berman KF, Callicott JH, Weinberger DR (2014) Altered hippocampal-parahippocampal function during stimulus encoding: a potential indicator of genetic liability for schizophrenia. JAMA Psychiatry 71:236–247
|
93 |
Ricciardi S, Ungaro F, Hambrock M, Rademacher N, Stefanelli G, Brambilla D, Sessa A, Magagnotti C, Bachi A, Giarda E
|
94 |
Rodrigues GMC, Gaj T, Adil MM, Wahba J, Rao AT, Lorbeer FK, Kulkarni RU, Diogo MM, Cabral JMS, Miller EW
|
95 |
Sakaguchi H, Kadoshima T, Soen M, Narii N, Ishida Y, Ohgushi M, Takahashi J, Eiraku M, Sasai Y (2015) Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue. Nat Commun 6:8896
|
96 |
Santos R, Vadodaria KC, Jaeger BN, Mei A, Lefcochilos-Fogelquist S, Mendes APD, Erikson G, Shokhirev M, Randolph-Moore L, Fredlender C
|
97 |
Sarkar A, Mei A, Paquola ACM, Stern S, Bardy C, Klug JR, Kim S, Neshat N, Kim HJ, Ku M
|
98 |
Schafer ST, Paquola ACM, Stern S, Gosselin D, Ku M, Pena M, Kuret TJM, Liyanage M, Mansour AA, Jaeger BN
|
99 |
Schizophrenia Working Group of the PsychiatricGenomics, C (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427
|
100 |
Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW
|
101 |
Sellgren CM, Gracias J, Watmuff B, Biag JD, Thanos JM, Whittredge PB, Fu T, Worringer K, Brown HE, Wang J
|
102 |
Shao Z, Noh H, Bin Kim W, Ni P, Nguyen C, Cote SE, Noyes E, Zhao J, Parsons T, Park JM
|
103 |
Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS (2010) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 28:152–163
|
104 |
Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R, Sebastiano V, Krawisz A, Froehlich W, Bernstein JA, Hallmayer JF
|
105 |
Shi Y, Inoue H, Wu JC, Yamanaka S (2017) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16:115–130
|
106 |
Shi Y, Kirwan P, Smith J, Robinson HP, Livesey FJ (2012) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15(477–486):S471
|
107 |
Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, Reimer R, Quake SR, Barres BA, Pasca SP (2017) Human astrocyte maturation captured in 3D cerebral cortical spheroids derived from pluripotent stem cells. Neuron 95(779–790):e776
|
108 |
Stern S, Santos R, Marchetto MC, Mendes APD, Rouleau GA, Biesmans S, Wang QW, Yao J, Charnay P, Bang AG
|
109 |
Sur M, Rubenstein JL (2005) Patterning and plasticity of the cerebral cortex. Science 310:805–810
|
110 |
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
|
111 |
Tamminga CA, Stan AD, Wagner AD (2010) The hippocampal formation in schizophrenia. Am J Psychiatry 167:1178–1193
|
112 |
Tao Y, Zhang SC (2016) Neural subtype specification from human pluripotent stem cells. Cell Stem Cell 19:573–586
|
113 |
Tekin S, Cummings JL (2002) Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 53:647–654
|
114 |
Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, Starkey M, Webster MJ, Yolken RH, Bahn S (2003) Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362:798–805
|
115 |
Vadodaria KC, Ji Y, Skime M, Paquola A, Nelson T, Hall-Flavin D, Fredlender C, Heard KJ, Deng Y, Le AT
|
116 |
Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474:380–384
|
117 |
Wang L, Xia J, Li J, Hagemann TL, Jones JR, Fraenkel E, Weitz DA, Zhang SC, Messing A, Feany MB (2018) Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nat Commun 9:1899
|
118 |
Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M
|
119 |
Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, Barrow AD, Diamond MS, Colonna M (2012) IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol 13:753–760
|
120 |
Watanabe K, Kamiya D, Nishiyama A, Katayama T, Nozaki S, Kawasaki H, Watanabe Y, Mizuseki K, Sasai Y (2005) Directed differentiation of telencephalic precursors from embryonic stem cells. Nat Neurosci 8:288–296
|
121 |
Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, Kim NS, Yoon KJ, Shin J, Zhang C
|
122 |
Wilson SW, Houart C (2004) Early steps in the development of the forebrain. Dev Cell 6:167–181
|
123 |
Wimmer RA, Leopoldi A, Aichinger M, Wick N, Hantusch B, Novatchkova M, Taubenschmid J, Hammerle M, Esk C, Bagley JA
|
124 |
Windrem MS, Osipovitch M, Liu Z, Bates J, Chandler-Militello D, Zou L, Munir J, Schanz S, McCoy K, Miller RH
|
125 |
Wonders CP, Anderson SA (2006) The origin and specification of cortical interneurons. Nat Rev Neurosci 7:687–696
|
126 |
Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, Adams MJ, Agerbo E, Air TM, Andlauer TMF
|
127 |
Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, Cakir B, Kim KY, Lombroso AP, Hwang SM
|
128 |
Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC
|
129 |
Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA, Wernig M (2013) Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol 31:434–439
|
130 |
Yoon KJ, Nguyen HN, Ursini G, Zhang F, Kim NS, Wen Z, Makri G, Nauen D, Shin JH, Park Y
|
131 |
Yu DX, Di Giorgio FP, Yao J, Marchetto MC, Brennand K, Wright R, Mei A, McHenry L, Lisuk D, Grasmick JM
|
132 |
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R
|
133 |
Zeisel A, Munoz-Manchado AB, Codeluppi S, Lonnerberg P, La Manno G, Jureus A, Marques S, Munguba H, He L, Betsholtz C
|
134 |
Zhang Z, Marro SG, Zhang Y, Arendt KL, Patzke C, Zhou B, Fair T, Yang N, Sudhof TC, Wernig M
|
135 |
Zhang ZN, Freitas BC, Qian H, Lux J, Acab A, Trujillo CA, Herai RH, Nguyen Huu VAWen JH, Joshi-Barr S
|
136 |
Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, Zheng D, Lachman HM (2015a) 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
|
137 |
Zhao T, Zhang ZN, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215
|
138 |
Zhao T, Zhang ZN, Westenskow PD, Todorova D, Hu Z, Lin T, Rong Z, Kim J, He J, Wang M
|
/
〈 | 〉 |