Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Modeling neurological diseases using iPSC-derived neural cells

iPSC modeling of neurological diseases

Abstract

Developing efficient models for neurological diseases enables us to uncover disease mechanisms and develop therapeutic strategies to treat them. Discovery of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the way of modeling human diseases, especially neurological diseases. Currently almost all types of neural cells, including but not limited to neural stem cells, neurons, astrocytes, oligodendrocytes and microglia, can be derived from iPSCs following developmental principles. These iPSC-derived neural cells provide valuable tools for studying neurological disease mechanisms, developing potential therapies, and deepening our understanding of the nervous system.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F (2007) Neuronal damage in brain inflammation. Arch Neurol 64:185–189

  2. Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9:17–23

  3. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U (2009) Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–1512

  4. Bradl M, Lassmann H (2010) Oligodendrocytes: biology and pathology. Acta Neuropathol 119:37–53

  5. Chailangkarn T, Trujillo CA, Freitas BC, Hrvoj-Mihic B, Herai RH, DX Y, Brown TT, Marchetto MC, Bardy C, McHenry L, Stefanacci L, Jarvinen A, Searcy YM, DeWitt M, Wong W, Lai P, Ard MC, Hanson KL, Romero S, Jacobs B, Dale AM, Dai L, Korenberg JR, Gage FH, Bellugi U, Halgren E, Semendeferi K, Muotri AR (2016) A human neurodevelopmental model for Williams syndrome. Nature 536:338–343

  6. Chen H, Qian K, Du Z, Cao J, Petersen A, Liu H, Blackbourn LW, Huang CL, Errigo A, Yin Y, Lu J, Ayala M, Zhang SC (2014) Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons. Cell Stem Cell 14:796–809

  7. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823

  8. Cooper O, Seo H, Andrabi S, Guardia-Laguarta C, Graziotto J, Sundberg M, McLean JR, Carrillo-Reid L, Xie Z, Osborn T, Hargus G, Deleidi M, Lawson T, Bogetofte H, Perez-Torres E, Clark L, Moskowitz C, Mazzulli J, Chen L, Volpicelli-Daley L, Romero N, Jiang H, Uitti RJ, Huang Z, Opala G, Scarffe LA, Dawson VL, Klein C, Feng J, Ross OA, Trojanowski JQ, Lee VM, Marder K, Surmeier DJ, Wszolek ZK, Przedborski S, Krainc D, Dawson TM, Isacson O (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med 4:141ra190

  9. Douvaras P, Wang J, Zimmer M, Hanchuk S, O'Bara MA, Sadiq S, Sim FJ, Goldman J, Fossati V (2014) Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Rep 3:250–259

  10. Du ZW, Chen H, Liu H, Lu J, Qian K, Huang CL, Zhong X, Fan F, Zhang SC (2015) Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells. Nat Commun 6:6626

  11. Duan L, Bhattacharyya BJ, Belmadani A, Pan L, Miller RJ, Kessler JA (2014) Stem cell derived basal forebrain cholinergic neurons from Alzheimer's disease patients are more susceptible to cell death. Mol Neurodegener 9:3

  12. Ehrlich M, Mozafari S, Glatza M, Starost L, Velychko S, Hallmann AL, Cui QL, Schambach A, Kim KP, Bachelin C, Marteyn A, Hargus G, Johnson RM, Antel J, Sterneckert J, Zaehres H, Scholer HR, Baron-Van Evercooren A, Kuhlmann T (2017) Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors. Proc Natl Acad Sci U S A 114:E2243–E2252

  13. Gage FH, Temple S (2013) Neural stem cells: generating and regenerating the brain. Neuron 80:588–601

  14. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845

  15. Goldman SA, Kuypers NJ (2015) How to make an oligodendrocyte. Development 142:3983–3995

  16. Hallmann AL, Arauzo-Bravo MJ, Mavrommatis L, Ehrlich M, Ropke A, Brockhaus J, Missler M, Sterneckert J, Scholer HR, Kuhlmann T, Zaehres H, Hargus G (2017) Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein. Sci Rep 7:42991

  17. Hu BY, Zhang SC (2009) Differentiation of spinal motor neurons from pluripotent human stem cells. Nat Protoc 4:1295–1304

  18. Hu BY, Du ZW, Li XJ, Ayala M, Zhang SC (2009) Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136:1443–1452

  19. Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 107:4335–4340

  20. Izrael M, Zhang P, Kaufman R, Shinder V, Ella R, Amit M, Itskovitz-Eldor J, Chebath J, Revel M (2007) Human oligodendrocytes derived from embryonic stem cells: effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci 34:310–323

  21. Jiang P, Chen C, Wang R, Chechneva OV, Chung SH, Rao MS, Pleasure DE, Liu Y, Zhang Q, Deng W (2013) hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury. Nat Commun 4:2196

  22. Jones VC, Atkinson-Dell R, Verkhratsky A, Mohamet L (2017) Aberrant iPSC-derived human astrocytes in Alzheimer's disease. Cell Death Dis 8:e2696

  23. Juopperi TA, Kim WR, Chiang CH, Yu H, Margolis RL, Ross CA, Ming GL, Song H (2012) Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington's disease patient cells. Mol Brain 5:17

  24. Kawabata S, Takano M, Numasawa-Kuroiwa Y, Itakura G, Kobayashi Y, Nishiyama Y, Sugai K, Nishimura S, Iwai H, Isoda M, Shibata S, Kohyama J, Iwanami A, Toyama Y, Matsumoto M, Nakamura M, Okano H (2016) Grafted human iPS cell-derived Oligodendrocyte precursor cells contribute to robust Remyelination of Demyelinated axons after spinal cord injury. Stem Cell Rep 6:1–8

  25. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553

  26. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467:285–290

  27. Kiskinis E, Sandoe J, Williams LA, Boulting GL, Moccia R, Wainger BJ, Han S, Peng T, Thams S, Mikkilineni S, Mellin C, Merkle FT, Davis-Dusenbery BN, Ziller M, Oakley D, Ichida J, Di Costanzo S, Atwater N, Maeder ML, Goodwin MJ, Nemesh J, Handsaker RE, Paull D, Noggle S, McCarroll SA, Joung JK, Woolf CJ, Brown RH, Eggan K (2014) Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell 14:781–795

  28. Krencik R, Zhang SC (2011) Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc 6:1710–1717

  29. Li XJ, Zhang X, Johnson MA, Wang ZB, Lavaute T, Zhang SC (2009) Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells. Development 136:4055–4063

  30. Li W, Sun W, Zhang Y, Wei W, Ambasudhan R, Xia P, Talantova M, Lin T, Kim J, Wang X, Kim WR, Lipton SA, Zhang K, Ding S (2011) Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors. Proc Natl Acad Sci U S A 108:8299–8304

  31. Liao MC, Muratore CR, Gierahn TM, Sullivan SE, Srikanth P, De Jager PL, Love JC, Young-Pearse TL (2016) Single-cell detection of secreted Abeta and sAPPalpha from human IPSC-derived neurons and Astrocytes. J Neurosci 36:1730–1746

  32. Liu H, Zhang SC (2011) Specification of neuronal and glial subtypes from human pluripotent stem cells. Cell Mol Life Sci 68:3995–4008

  33. Liu Y, Jiang P, Deng W (2011) OLIG gene targeting in human pluripotent stem cells for motor neuron and oligodendrocyte differentiation. Nat Protoc 6:640–655

  34. Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W, Wagner U, Kim A, Ren B, Li Y, Goebl A, Kim J, Soligalla RD, Dubova I, Thompson J, Yates J 3rd, Esteban CR, Sancho-Martinez I, Izpisua Belmonte JC (2012) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491:603–607

  35. 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

  36. Liu Q, Waltz S, Woodruff G, Ouyang J, Israel MA, Herrera C, Sarsoza F, Tanzi RE, Koo EH, Ringman JM, Goldstein LS, Wagner SL, Yuan SH (2014) Effect of potent gamma-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers. JAMA Neurol 71:1481–1489

  37. Marignier R, Nicolle A, Watrin C, Touret M, Cavagna S, Varrin-Doyer M, Cavillon G, Rogemond V, Confavreux C, Honnorat J, Giraudon P (2010) Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain J neurol 133:2578–2591

  38. Mayshar Y, Ben-David U, Lavon N, Biancotti JC, Yakir B, Clark AT, Plath K, Lowry WE, Benvenisty N (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7:521–531

  39. Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, EY T, Mandal PK, Vera E, Shim JW, Kriks S, Taldone T, Fusaki N, Tomishima MJ, Krainc D, Milner TA, Rossi DJ, Studer L (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13:691–705

  40. Milner R, Frost E, Nishimura S, Delcommenne M, Streuli C, Pytela R, Ffrench-Constant C (1997) Expression of alpha vbeta3 and alpha vbeta8 integrins during oligodendrocyte precursor differentiation in the presence and absence of axons. Glia 21:350–360

  41. Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K, Nakagawa M, Koyanagi M, Tanabe K, Ohnuki M, Ogawa D, Ikeda E, Okano H, Yamanaka S (2009) Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 27:743–745

  42. Moscou MJ, Bogdanove AJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326:1501

  43. Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM, Jaenisch R (2016) Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 22:1358–1367

  44. Mungenast AE, Siegert S, Tsai LH (2016) Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells. Mol Cell Neurosci 73:13–31

  45. Murai K, Sun G, Ye P, Tian E, Yang S, Cui Q, Sun G, Trinh D, Sun O, Hong T, Wen Z, Kalkum M, Riggs AD, Song H, Ming GL, Shi Y (2016) The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model. Nat Commun 7:10965

  46. Nevin ZS, Factor DC, Karl RT, Douvaras P, Laukka J, Windrem MS, Goldman SA, Fossati V, Hobson GM, Tesar PJ (2017) Modeling the mutational and phenotypic landscapes of Pelizaeus-Merzbacher disease with human iPSC-derived Oligodendrocytes. Am J Hum Genet 100:617–634

  47. Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee K, Schule B, Dolmetsch RE, Langston W, Palmer TD, Pera RR (2011) LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8:267–280

  48. Niehaus A, Stegmuller J, Diers-Fenger M, Trotter J (1999) Cell-surface glycoprotein of oligodendrocyte progenitors involved in migration. J Neurosci 19:4948–4961

  49. Numasawa-Kuroiwa Y, Okada Y, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Osaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H (2014) Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes. Stem Cell Rep 2:648–661

  50. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

  51. Pandya H, Shen MJ, Ichikawa DM, Sedlock AB, Choi Y, Johnson KR, Kim G, Brown MA, Elkahloun AG, Maric D, Sweeney CL, Gossa S, Malech HL, McGavern DB, Park JK (2017) Differentiation of human and murine induced pluripotent stem cells to microglia-like cells. Nat Neurosci (in press)

  52. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–1458

  53. Pekny M, Pekna M, Messing A, Steinhauser C, Lee JM, Parpura V, Hol EM, Sofroniew MV, Verkhratsky A (2016) Astrocytes: a central element in neurological diseases. Acta Neuropathol 131:323–345

  54. Prinz M, Priller J (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci 15:300–312

  55. Quinlan RA, Brenner M, Goldman JE, Messing A (2007) GFAP and its role in Alexander disease. Exp Cell Res 313:2077–2087

  56. Roybon L, Lamas NJ, Garcia-Diaz A, Yang EJ, Sattler R, Jackson-Lewis V, Kim YA, Kachel CA, Rothstein JD, Przedborski S, Wichterle H, Henderson CE (2013) Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes. Cell Rep 4:1035–1048

  57. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90

  58. Serio A, Bilican B, Barmada SJ, Ando DM, Zhao C, Siller R, Burr K, Haghi G, Story D, Nishimura AL, Carrasco MA, Phatnani HP, Shum C, Wilmut I, Maniatis T, Shaw CE, Finkbeiner S, Chandran S (2013) Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc Natl Acad Sci U S A 110:4697–4702

  59. Shaltouki A, Peng J, Liu Q, Rao MS, Zeng X (2013) Efficient generation of astrocytes from human pluripotent stem cells in defined conditions. Stem Cells 31:941–952

  60. Shi Y, Inoue H, JC W, Yamanaka S (2017) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16:115–130

  61. Singh I, Pahan K, Khan M, Singh AK (1998) Cytokine-mediated induction of ceramide production is redox-sensitive. Implications to proinflammatory cytokine-mediated apoptosis in demyelinating diseases. J Biol Chem 273:20354–20362

  62. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

  63. Spassky N, Heydon K, Mangatal A, Jankovski A, Olivier C, Queraud-Lesaux F, Goujet-Zalc C, Thomas JL, Zalc B (2001) Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRalpha signaling. Development 128:4993–5004

  64. Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R (2010) Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell 7:20–24

  65. Taapken SM, Nisler BS, Newton MA, Sampsell-Barron TL, Leonhard KA, McIntire EM, Montgomery KD (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat Biotechnol 29:313–314

  66. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

  67. 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

  68. Thiruvalluvan A, Czepiel M, Kap YA, Mantingh-Otter I, Vainchtein I, Kuipers J, Bijlard M, Baron W, Giepmans B, Bruck W, t Hart BA, Boddeke E, Copray S (2016) Survival and functionality of human induced Pluripotent stem cell-derived Oligodendrocytes in a nonhuman primate model for multiple sclerosis. Stem Cells Transl Med 5:1550–1561

  69. Tsai HH, Tessier-Lavigne M, Miller RH (2003) Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal. Development 130:2095–2105

  70. Waisman A, Ginhoux F, Greter M, Bruttger J (2015) Homeostasis of microglia in the adult brain: review of novel microglia depletion systems. Trends Immunol 36:625–636

  71. Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA (2013) Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 12:252–264

  72. Wiedenheft B, Sternberg SH, Doudna JA (2012) RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331–338

  73. Woodard CM, Campos BA, Kuo SH, Nirenberg MJ, Nestor MW, Zimmer M, Mosharov EV, Sulzer D, Zhou H, Paull D, Clark L, Schadt EE, Sardi SP, Rubin L, Eggan K, Brock M, Lipnick S, Rao M, Chang S, Li A, Noggle SA (2014) iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson's disease. Cell Rep 9:1173–1182

  74. Xu Q, Guo L, Moore H, Waclaw RR, Campbell K, Anderson SA (2010) Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron 65:328–340

  75. Yao H, Azad P, Zhao HW, Wang J, Poulsen O, Freitas BC, Muotri AR, Haddad GG (2016) The Na+/HCO3- co-transporter is protective during ischemia in astrocytes. Neuroscience 339:329–337

  76. Yoon KJ, Nguyen HN, Ursini G, Zhang F, Kim NS, Wen Z, Makri G, Nauen D, Shin JH, Park Y, Chung R, Pekle E, Zhang C, Towe M, Hussaini SM, Lee Y, Rujescu D, St Clair D, Kleinman JE, Hyde TM, Krauss G, Christian KM, Rapoport JL, Weinberger DR, Song H, Ming GL (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

  77. Zhang ZN, Freitas BC, Qian H, Lux J, Acab A, Trujillo CA, Herai RH, Nguyen Huu VA, Wen JH, Joshi-Barr S, Karpiak JV, Engler AJ, Fu XD, Muotri AR, Almutairi A (2016) Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction. Proc Natl Acad Sci U S A 113:3185–3190

  78. Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, Wang Y, Zhang Y, Zhuang Q, Li Y, Bao X, Tse HF, Grillari J, Grillari-Voglauer R, Pei D, Esteban MA (2012) Generation of human induced pluripotent stem cells from urine samples. Nat Protoc 7:2080–2089

Download references

Acknowledgements

This work was supported by the Herbert Horvitz Family, Sidell Kagan Foundation, California Institute for Regenerative Medicine TRAN1-08525, and the National Institute of Aging of the National Institutes of Health R01AG056305. J.C is a Herbert Horvitz Fellow. Research reported in this publication was also supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Correspondence to Yanhong Shi.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, L., Chao, J. & Shi, Y. Modeling neurological diseases using iPSC-derived neural cells. Cell Tissue Res 371, 143–151 (2018). https://doi.org/10.1007/s00441-017-2713-x

Download citation

Keywords

  • iPSC
  • Neurological diseases
  • Disease modeling