{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:05:18Z","timestamp":1792663518661,"version":"4.5.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Huntington\u2019s Disease (HD) is a devastating neurodegenerative disorder that clinically manifests as motor dysfunction, cognitive impairment and psychiatric symptoms. There is currently no cure for this progressive and fatal disorder. The causative mutation of this hereditary disease is a trinucleotide repeat expansion (CAG) in the Huntingtin gene that results in an expanded polyglutamine tract. Multiple mechanisms have been proposed to explain the preferential striatal and cortical degeneration that occurs with HD, including non-cell-autonomous contribution from astrocytes. Although numerous cell culture and animal models exist, there is a great need for experimental systems that can more accurately replicate the human disease. Human induced pluripotent stem cells (iPSCs) are a remarkable new tool to study neurological disorders because this cell type can be derived from patients as a renewable, genetically tractable source for unlimited cells that are difficult to acquire, such as neurons and astrocytes. The development of experimental systems based on iPSC technology could aid in the identification of molecular lesions and therapeutic treatments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We derived iPSCs from a father with adult onset HD and 50 CAG repeats (F-HD-iPSC) and his daughter with juvenile HD and 109 CAG repeats (D-HD-iPSC). These disease-specific iPSC lines were characterized by standard assays to assess the quality of iPSC lines and to demonstrate their pluripotency. HD-iPSCs were capable of producing phenotypically normal, functional neurons <jats:italic>in vitro<\/jats:italic> and were able to survive and differentiate into neurons in the adult mouse brain <jats:italic>in vivo<\/jats:italic> after transplantation. Surprisingly, when HD-iPSCs were directed to differentiate into an astrocytic lineage, we observed the presence of cytoplasmic, electron clear vacuoles in astrocytes from both F-HD-iPSCs and D-HD-iPSCs, which were significantly more pronounced in D-HD-astrocytes. Remarkably, the vacuolation in diseased astrocytes was observed under basal culture conditions without additional stressors and increased over time. Importantly, similar vacuolation phenotype has also been observed in peripheral blood lymphocytes from individuals with HD. Together, these data suggest that vacuolation may be a phenotype associated with HD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have generated a unique <jats:italic>in vitro<\/jats:italic> system to study HD pathogenesis using patient-specific iPSCs. The astrocytes derived from patient-specific iPSCs exhibit a vacuolation phenotype, a phenomenon previously documented in primary lymphocytes from HD patients. Our studies pave the way for future mechanistic investigations using human iPSCs to model HD and for high-throughput therapeutic screens.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-6606-5-17","type":"journal-article","created":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T12:14:44Z","timestamp":1337602484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":201,"title":["Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington\u2019s disease patient cells"],"prefix":"10.1186","volume":"5","author":[{"given":"Tarja A","family":"Juopperi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woon Ryoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsuan","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell L","family":"Margolis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-li","family":"Ming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,5,21]]},"reference":[{"issue":"9","key":"174_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.tibs.2006.06.009","volume":"31","author":"JF Gusella","year":"2006","unstructured":"Gusella JF, MacDonald ME: Huntington\u2019s disease: seeing the pathogenic process through a genetic lens. Trends Biochem Sci. 2006, 31 (9): 533-540. 10.1016\/j.tibs.2006.06.009.","journal-title":"Trends Biochem Sci"},{"issue":"1","key":"174_CR2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","volume":"10","author":"CA Ross","year":"2011","unstructured":"Ross CA, Tabrizi SJ: Huntington\u2019s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011, 10 (1): 83-98. 10.1016\/S1474-4422(10)70245-3.","journal-title":"Lancet Neurol"},{"key":"174_CR3","doi-asserted-by":"crossref","unstructured":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes. Cell. 1993, 72 (6): 971-983. 10.1016\/0092-8674(93)90585-E.","DOI":"10.1016\/0092-8674(93)90585-E"},{"issue":"5334","key":"174_CR4","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","volume":"277","author":"M DiFiglia","year":"1997","unstructured":"DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N: Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 1997, 277 (5334): 1990-1993. 10.1126\/science.277.5334.1990.","journal-title":"Science"},{"issue":"2","key":"174_CR5","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1042\/BJ20071619","volume":"412","author":"S Imarisio","year":"2008","unstructured":"Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, et al: Huntington\u2019s disease: from pathology and genetics to potential therapies. Biochem J. 2008, 412 (2): 191-209. 10.1042\/BJ20071619.","journal-title":"Biochem J"},{"issue":"5","key":"174_CR6","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/0896-6273(95)90345-3","volume":"14","author":"AH Sharp","year":"1995","unstructured":"Sharp AH, Loev SJ, Schilling G, Li SH, Li XJ, Bao J, Wagster MV, Kotzuk JA, Steiner JP, Lo A, et al: Widespread expression of Huntington\u2019s disease gene (IT15) protein product. Neuron. 1995, 14 (5): 1065-1074. 10.1016\/0896-6273(95)90345-3.","journal-title":"Neuron"},{"issue":"4","key":"174_CR7","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/78054","volume":"25","author":"H Li","year":"2000","unstructured":"Li H, Li SH, Johnston H, Shelbourne PF, Li XJ: Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat Genet. 2000, 25 (4): 385-389. 10.1038\/78054.","journal-title":"Nat Genet"},{"issue":"2","key":"174_CR8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1006\/exnr.1998.6778","volume":"150","author":"SK Singhrao","year":"1998","unstructured":"Singhrao SK, Thomas P, Wood JD, MacMillan JC, Neal JW, Harper PS, Jones AL: Huntingtin protein colocalizes with lesions of neurodegenerative diseases: an investigation in Huntington\u2019s, Alzheimer\u2019s, and Pick\u2019s diseases. Exp Neurol. 1998, 150 (2): 213-222. 10.1006\/exnr.1998.6778.","journal-title":"Exp Neurol"},{"issue":"6","key":"174_CR9","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1083\/jcb.200508072","volume":"171","author":"JY Shin","year":"2005","unstructured":"Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ: Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol. 2005, 171 (6): 1001-1012. 10.1083\/jcb.200508072.","journal-title":"J Cell Biol"},{"issue":"1","key":"174_CR10","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00401-007-0306-6","volume":"115","author":"JP Vonsattel","year":"2008","unstructured":"Vonsattel JP: Huntington disease models and human neuropathology: similarities and differences. Acta Neuropathol. 2008, 115 (1): 55-69.","journal-title":"Acta Neuropathol"},{"issue":"4688","key":"174_CR11","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/science.3155875","volume":"227","author":"GA Graveland","year":"1985","unstructured":"Graveland GA, Williams RS, DiFiglia M: Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington\u2019s disease. Science. 1985, 227 (4688): 770-773. 10.1126\/science.3155875.","journal-title":"Science"},{"issue":"5","key":"174_CR12","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1136\/jnnp.56.5.487","volume":"56","author":"E Spargo","year":"1993","unstructured":"Spargo E, Everall IP, Lantos PL: Neuronal loss in the hippocampus in Huntington\u2019s disease: a comparison with HIV infection. J Neurol Neurosurg Psychiatry. 1993, 56 (5): 487-491. 10.1136\/jnnp.56.5.487.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"10","key":"174_CR13","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1373\/49.10.1726","volume":"49","author":"RL Margolis","year":"2003","unstructured":"Margolis RL, Ross CA: Diagnosis of huntington disease. Clin Chem. 2003, 49 (10): 1726-1732. 10.1373\/49.10.1726.","journal-title":"Clin Chem"},{"issue":"1","key":"174_CR14","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1212\/WNL.0b013e318249f683","volume":"78","author":"RE Lee JM","year":"2012","unstructured":"Lee JM RE, Lee JH, Gillis T, Mysore JS, Hayden MR, Warby SC, Morrison PNM, Ross CA, Margolis RL, Squitieri F, Orobello S, Di Donato S, Gomez-Tortosa EAC, Suchowersky O, Trent RJ, McCusker E, Novelletto A, Frontali MJR, Ashizawa T, Frank S, Saint-Hilaire MH, Hersch SM, Rosas HD, Lucente DHM, Zanko A, Abramson RK, Marder K, Sequeiros J, Paulsen JS, on behalf of the PREDICT-HD study of the Huntington Study Group (HSG), Huntington\u2019s LGobotRsotE, Disease Network MRobotH-MSG, Macdonald ME, HSG. GJobotCsot: CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion. Neurology. 2012, 78 (1): 690-695. 10.1212\/WNL.0b013e318249f683.","journal-title":"Neurology"},{"issue":"3","key":"174_CR15","first-page":"593","volume":"57","author":"NG Ranen","year":"1995","unstructured":"Ranen NG, Stine OC, Abbott MH, Sherr M, Codori AM, Franz ML, Chao NI, Chung AS, Pleasant N, Callahan C, et al: Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am J Hum Genet. 1995, 57 (3): 593-602.","journal-title":"Am J Hum Genet"},{"issue":"4","key":"174_CR16","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/ng0893-398","volume":"4","author":"SE Andrew","year":"1993","unstructured":"Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA, et al: The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington\u2019s disease. Nat Genet. 1993, 4 (4): 398-403. 10.1038\/ng0893-398.","journal-title":"Nat Genet"},{"issue":"1","key":"174_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S1472-6483(10)60053-3","volume":"19","author":"JC Niclis","year":"2009","unstructured":"Niclis JC, Trounson AO, Dottori M, Ellisdon AM, Bottomley SP, Verlinsky Y, Cram DS: Human embryonic stem cell models of Huntington disease. Reprod Biomed Online. 2009, 19 (1): 106-113. 10.1016\/S1472-6483(10)60053-3.","journal-title":"Reprod Biomed Online"},{"issue":"3","key":"174_CR18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1089\/scd.2010.0120","volume":"20","author":"CK Bradley","year":"2011","unstructured":"Bradley CK, Scott HA, Chami O, Peura TT, Dumevska B, Schmidt U, Stojanov T: Derivation of Huntington\u2019s disease-affected human embryonic stem cell lines. Stem Cells Dev. 2011, 20 (3): 495-502. 10.1089\/scd.2010.0120.","journal-title":"Stem Cells Dev"},{"issue":"1","key":"174_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2008.06.005","volume":"32","author":"MY Heng","year":"2008","unstructured":"Heng MY, Detloff PJ, Albin RL: Rodent genetic models of Huntington disease. Neurobiol Dis. 2008, 32 (1): 1-9. 10.1016\/j.nbd.2008.06.005.","journal-title":"Neurobiol Dis"},{"issue":"3","key":"174_CR20","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/S0092-8674(00)80513-9","volume":"90","author":"SW Davies","year":"1997","unstructured":"Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP: Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 1997, 90 (3): 537-548. 10.1016\/S0092-8674(00)80513-9.","journal-title":"Cell"},{"issue":"11","key":"174_CR21","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nrd3556","volume":"10","author":"DE Ehrnhoefer","year":"2011","unstructured":"Ehrnhoefer DE, Wong BK, Hayden MR: Convergent pathogenic pathways in Alzheimer\u2019s and Huntington\u2019s diseases: shared targets for drug development. Nat Rev Drug Discov. 2011, 10 (11): 853-867. 10.1038\/nrd3556.","journal-title":"Nat Rev Drug Discov"},{"issue":"52","key":"174_CR22","doi-asserted-by":"publisher","first-page":"22480","DOI":"10.1073\/pnas.0911503106","volume":"106","author":"J Bradford","year":"2009","unstructured":"Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S: Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A. 2009, 106 (52): 22480-22485. 10.1073\/pnas.0911503106.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"174_CR23","doi-asserted-by":"publisher","first-page":"10653","DOI":"10.1074\/jbc.M109.083287","volume":"285","author":"J Bradford","year":"2010","unstructured":"Bradford J, Shin JY, Roberts M, Wang CE, Sheng G, Li S, Li XJ: Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. J Biol Chem. 2010, 285 (14): 10653-10661. 10.1074\/jbc.M109.083287.","journal-title":"J Biol Chem"},{"issue":"15","key":"174_CR24","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1093\/hmg\/ddq212","volume":"19","author":"M Faideau","year":"2010","unstructured":"Faideau M, Kim J, Cormier K, Gilmore R, Welch M, Auregan G, Dufour N, Guillermier M, Brouillet E, Hantraye P, et al: In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington\u2019s disease subjects. Hum Mol Genet. 2010, 19 (15): 3053-3067. 10.1093\/hmg\/ddq212.","journal-title":"Hum Mol Genet"},{"issue":"32","key":"174_CR25","doi-asserted-by":"publisher","first-page":"10844","DOI":"10.1523\/JNEUROSCI.0917-10.2010","volume":"30","author":"M Valenza","year":"2010","unstructured":"Valenza M, Leoni V, Karasinska JM, Petricca L, Fan J, Carroll J, Pouladi MA, Fossale E, Nguyen HP, Riess O, et al: Cholesterol defect is marked across multiple rodent models of Huntington\u2019s disease and is manifest in astrocytes. J Neurosci. 2010, 30 (32): 10844-10850. 10.1523\/JNEUROSCI.0917-10.2010.","journal-title":"J Neurosci"},{"issue":"4","key":"174_CR26","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","volume":"126","author":"K Takahashi","year":"2006","unstructured":"Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006, 126 (4): 663-676. 10.1016\/j.cell.2006.07.024.","journal-title":"Cell"},{"issue":"5","key":"174_CR27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007, 131 (5): 861-872. 10.1016\/j.cell.2007.11.019.","journal-title":"Cell"},{"issue":"1","key":"174_CR28","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.stem.2010.06.002","volume":"7","author":"J Staerk","year":"2010","unstructured":"Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R: Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell. 2010, 7 (1): 20-24. 10.1016\/j.stem.2010.06.002.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"174_CR29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.stem.2010.06.003","volume":"7","author":"T Seki","year":"2010","unstructured":"Seki T, Yuasa S, Oda M, Egashira T, Yae K, Kusumoto D, Nakata H, Tohyama S, Hashimoto H, Kodaira M, et al: Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell. 2010, 7 (1): 11-14. 10.1016\/j.stem.2010.06.003.","journal-title":"Cell Stem Cell"},{"issue":"5391","key":"174_CR30","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","volume":"282","author":"JA Thomson","year":"1998","unstructured":"Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 1998, 282 (5391): 1145-1147.","journal-title":"Science"},{"issue":"3","key":"174_CR31","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2217\/fnl.11.14","volume":"6","author":"TA Juopperi","year":"2011","unstructured":"Juopperi TA, Song H, Ming GL: Modeling neurological diseases using patient-derived induced pluripotent stem cells. Future Neurol. 2011, 6 (3): 363-373. 10.2217\/fnl.11.14.","journal-title":"Future Neurol"},{"issue":"7384","key":"174_CR32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10821","volume":"482","author":"MA Israel","year":"2012","unstructured":"Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, et al: Probing sporadic and familial Alzheimer\u2019s disease using induced pluripotent stem cells. Nature. 2012, 482 (7384): 216-220.","journal-title":"Nature"},{"issue":"4","key":"174_CR33","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S1474-4422(11)70022-9","volume":"10","author":"VB Mattis","year":"2011","unstructured":"Mattis VB, Svendsen CN: Induced pluripotent stem cells: a new revolution for clinical neurology?. Lancet Neurol. 2011, 10 (4): 383-394. 10.1016\/S1474-4422(11)70022-9.","journal-title":"Lancet Neurol"},{"issue":"23","key":"174_CR34","doi-asserted-by":"publisher","first-page":"4530","DOI":"10.1093\/hmg\/ddr394","volume":"20","author":"T Yagi","year":"2011","unstructured":"Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T, Yamanaka S, Okano H, Suzuki N: Modeling familial Alzheimer\u2019s disease with induced pluripotent stem cells. Hum Mol Genet. 2011, 20 (23): 4530-4539. 10.1093\/hmg\/ddr394.","journal-title":"Hum Mol Genet"},{"issue":"45","key":"174_CR35","doi-asserted-by":"publisher","first-page":"16070","DOI":"10.1523\/JNEUROSCI.4218-11.2011","volume":"31","author":"GL Ming","year":"2011","unstructured":"Ming GL, Brustle O, Muotri A, Studer L, Wernig M, Christian KM: Cellular reprogramming: recent advances in modeling neurological diseases. J Neurosci. 2011, 31 (45): 16070-16075. 10.1523\/JNEUROSCI.4218-11.2011.","journal-title":"J Neurosci"},{"issue":"34","key":"174_CR36","doi-asserted-by":"publisher","first-page":"13821","DOI":"10.1073\/pnas.0706199104","volume":"104","author":"H Wu","year":"2007","unstructured":"Wu H, Xu J, Pang ZP, Ge W, Kim KJ, Blanchi B, Chen C, Sudhof TC, Sun YE: Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proc Natl Acad Sci U S A. 2007, 104 (34): 13821-13826. 10.1073\/pnas.0706199104.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"174_CR37","first-page":"153","volume":"331","author":"M Carpenter","year":"2006","unstructured":"Carpenter M, Rao MS, Freed W, Zeng X: Derivation and characterization of neuronal precursors and dopaminergic neurons from human embryonic stem cells in vitro. Methods Mol Biol. 2006, 331: 153-167.","journal-title":"Methods Mol Biol"},{"issue":"6","key":"174_CR38","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1634\/stemcells.2008-0039","volume":"26","author":"T Vazin","year":"2008","unstructured":"Vazin T, Chen J, Lee CT, Amable R, Freed WJ: Assessment of stromal-derived inducing activity in the generation of dopaminergic neurons from human embryonic stem cells. Stem Cells. 2008, 26 (6): 1517-1525. 10.1634\/stemcells.2008-0039.","journal-title":"Stem Cells"},{"issue":"5","key":"174_CR39","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nn844","volume":"5","author":"HJ Song","year":"2002","unstructured":"Song HJ, Stevens CF, Gage FH: Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat Neurosci. 2002, 5 (5): 438-445.","journal-title":"Nat Neurosci"},{"issue":"4","key":"174_CR40","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.neuron.2011.05.001","volume":"70","author":"GL Ming","year":"2011","unstructured":"Ming GL, Song H: Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011, 70 (4): 687-702. 10.1016\/j.neuron.2011.05.001.","journal-title":"Neuron"},{"issue":"Pt 13","key":"174_CR41","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1242\/jcs.01131","volume":"117","author":"Y Kabeya","year":"2004","unstructured":"Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T: LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004, 117 (Pt 13): 2805-2812.","journal-title":"J Cell Sci"},{"issue":"6","key":"174_CR42","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.stem.2008.11.008","volume":"3","author":"N Maherali","year":"2008","unstructured":"Maherali N, Hochedlinger K: Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008, 3 (6): 595-605. 10.1016\/j.stem.2008.11.008.","journal-title":"Cell Stem Cell"},{"key":"174_CR43","unstructured":"Induced pluripotent stem cells from patiwnts with Huntington\u2019s Disease show CAG repeat expansion associated phenotypes. Cell Stem Cell. 2012, In press"},{"key":"174_CR44","doi-asserted-by":"publisher","first-page":"RRN1193","DOI":"10.1371\/currents.RRN1193","volume":"2","author":"N Zhang","year":"2010","unstructured":"Zhang N, An MC, Montoro D, Ellerby LM: Characterization of human Huntington\u2019s disease cell model from induced pluripotent stem cells. PLoS Curr. 2010, 2: RRN1193-","journal-title":"PLoS Curr"},{"issue":"5","key":"174_CR45","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.cell.2009.02.013","volume":"136","author":"F Soldner","year":"2009","unstructured":"Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, et al: Parkinson\u2019s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009, 136 (5): 964-977. 10.1016\/j.cell.2009.02.013.","journal-title":"Cell"},{"issue":"5893","key":"174_CR46","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1126\/science.1158799","volume":"321","author":"JT Dimos","year":"2008","unstructured":"Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, et al: Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008, 321 (5893): 1218-1221. 10.1126\/science.1158799.","journal-title":"Science"},{"issue":"6884","key":"174_CR47","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/417039a","volume":"417","author":"H Song","year":"2002","unstructured":"Song H, Stevens CF, Gage FH: Astroglia induce neurogenesis from adult neural stem cells. Nature. 2002, 417 (6884): 39-44. 10.1038\/417039a.","journal-title":"Nature"},{"issue":"4","key":"174_CR48","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrn2803","volume":"11","author":"NB Hamilton","year":"2010","unstructured":"Hamilton NB, Attwell D: Do astrocytes really exocytose neurotransmitters?. Nat Rev Neurosci. 2010, 11 (4): 227-238. 10.1038\/nrn2803.","journal-title":"Nat Rev Neurosci"},{"issue":"6","key":"174_CR49","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.stem.2008.09.017","volume":"3","author":"FP Di Giorgio","year":"2008","unstructured":"Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC: Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell. 2008, 3 (6): 637-648. 10.1016\/j.stem.2008.09.017.","journal-title":"Cell Stem Cell"},{"issue":"5","key":"174_CR50","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/nn1885","volume":"10","author":"FP Di Giorgio","year":"2007","unstructured":"Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K: Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007, 10 (5): 608-614. 10.1038\/nn1885.","journal-title":"Nat Neurosci"},{"issue":"1","key":"174_CR51","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/mds.23455","volume":"26","author":"GM Halliday","year":"2011","unstructured":"Halliday GM, Stevens CH: Glia: initiators and progressors of pathology in Parkinson\u2019s disease. Mov Disord. 2011, 26 (1): 6-17. 10.1002\/mds.23455.","journal-title":"Mov Disord"},{"issue":"3","key":"174_CR52","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JAD-2010-101089","volume":"22","author":"AJ Vincent","year":"2010","unstructured":"Vincent AJ, Gasperini R, Foa L, Small DH: Astrocytes in Alzheimer\u2019s disease: emerging roles in calcium dysregulation and synaptic plasticity. J Alzheimers Dis. 2010, 22 (3): 699-714.","journal-title":"J Alzheimers Dis"},{"key":"174_CR53","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.brainres.2012.01.077","volume":"1449","author":"L Wang","year":"2012","unstructured":"Wang L, Lin F, Wang J, Wu J, Han R, Zhu L, Difiglia M, Qin Z: Expression of mutant N-terminal huntingtin fragment (htt552-100Q) in astrocytes suppresses the secretion of BDNF. Brain Res. 2012, 1449: 69-82.","journal-title":"Brain Res"},{"issue":"8","key":"174_CR54","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1097\/01.wnr.0000127073.66692.8f","volume":"15","author":"E Nagata","year":"2004","unstructured":"Nagata E, Sawa A, Ross CA, Snyder SH: Autophagosome-like vacuole formation in Huntington\u2019s disease lymphoblasts. Neuroreport. 2004, 15 (8): 1325-1328. 10.1097\/01.wnr.0000127073.66692.8f.","journal-title":"Neuroreport"},{"issue":"5","key":"174_CR55","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/nn.2528","volume":"13","author":"M Martinez-Vicente","year":"2010","unstructured":"Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, Kaushik S, de Vries R, Arias E, Harris S, Sulzer D, et al: Cargo recognition failure is responsible for inefficient autophagy in Huntington\u2019s disease. Nat Neurosci. 2010, 13 (5): 567-576. 10.1038\/nn.2528.","journal-title":"Nat Neurosci"},{"issue":"7227","key":"174_CR56","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature07677","volume":"457","author":"AD Ebert","year":"2009","unstructured":"Ebert AD, Yu J, Rose FF, Mattis VB, Lorson CL, Thomson JA, Svendsen CN: Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009, 457 (7227): 277-280. 10.1038\/nature07677.","journal-title":"Nature"},{"issue":"4","key":"174_CR57","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.cell.2010.10.016","volume":"143","author":"MC Marchetto","year":"2010","unstructured":"Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR: A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010, 143 (4): 527-539. 10.1016\/j.cell.2010.10.016.","journal-title":"Cell"},{"issue":"7262","key":"174_CR58","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/nature08320","volume":"461","author":"G Lee","year":"2009","unstructured":"Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, et al: Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. 2009, 461 (7262): 402-406. 10.1038\/nature08320.","journal-title":"Nature"},{"issue":"4","key":"174_CR59","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/mp.2011.13","volume":"16","author":"CH Chiang","year":"2011","unstructured":"Chiang CH, Su Y, Wen Z, Yoritomo N, Ross CA, Margolis RL, Song H, Ming GL: Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol Psychiatry. 2011, 16 (4): 358-360. 10.1038\/mp.2011.13.","journal-title":"Mol Psychiatry"},{"key":"174_CR60","first-page":"Unit 4A 2","volume":"Chapter 4","author":"M Ohnuki","year":"2009","unstructured":"Ohnuki M, Takahashi K, Yamanaka S: Generation and characterization of human induced pluripotent stem cells. Curr Protoc Stem Cell Biol. 2009, Chapter 4: Unit 4A 2-","journal-title":"Curr Protoc Stem Cell Biol"},{"issue":"8","key":"174_CR61","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1634\/stemcells.2008-0388","volume":"26","author":"DK Ma","year":"2008","unstructured":"Ma DK, Chiang CH, Ponnusamy K, Ming GL, Song H: G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells. Stem Cells. 2008, 26 (8): 2131-2141. 10.1634\/stemcells.2008-0388.","journal-title":"Stem Cells"},{"issue":"1","key":"174_CR62","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1089\/scd.2007.0266","volume":"18","author":"TA Prokhorova","year":"2009","unstructured":"Prokhorova TA, Harkness LM, Frandsen U, Ditzel N, Schroder HD, Burns JS, Kassem M: Teratoma formation by human embryonic stem cells is site dependent and enhanced by the presence of matrigel. Stem Cells Dev. 2009, 18 (1): 47-54. 10.1089\/scd.2007.0266.","journal-title":"Stem Cells Dev"},{"issue":"7076","key":"174_CR63","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/nature04404","volume":"439","author":"S Ge","year":"2006","unstructured":"Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H: GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature. 2006, 439 (7076): 589-593. 10.1038\/nature04404.","journal-title":"Nature"},{"issue":"6","key":"174_CR64","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.cell.2007.07.010","volume":"130","author":"X Duan","year":"2007","unstructured":"Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y, Liu XB, Yang CH, Jordan JD, Ma DK, et al: Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell. 2007, 130 (6): 1146-1158. 10.1016\/j.cell.2007.07.010.","journal-title":"Cell"},{"issue":"7","key":"174_CR65","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.cell.2011.05.024","volume":"145","author":"MA Bonaguidi","year":"2011","unstructured":"Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, Song H: In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell. 2011, 145 (7): 1142-1155. 10.1016\/j.cell.2011.05.024.","journal-title":"Cell"},{"issue":"5","key":"174_CR66","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.cell.2011.12.037","volume":"148","author":"JY Kim","year":"2012","unstructured":"Kim JY, Liu CY, Zhang F, Duan X, Wen Z, Song J, Feighery E, Lu B, Rujescu D, Clair D, et al: Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell. 2012, 148 (5): 1051-1064. 10.1016\/j.cell.2011.12.037.","journal-title":"Cell"}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1756-6606-5-17.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T20:38:26Z","timestamp":1630528706000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularbrain.biomedcentral.com\/articles\/10.1186\/1756-6606-5-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,21]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["174"],"URL":"https:\/\/doi.org\/10.1186\/1756-6606-5-17","relation":{},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,21]]},"assertion":[{"value":"21 April 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"17"}}