{"id":"https://openalex.org/W2519967434","doi":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","title":"Chemical Control of Grafted Human Pluripotent Stem Cell\u2013Derived Neurons in a Mouse Parkinson Disease Model","display_name":"Chemical Control of Grafted Human Pluripotent Stem Cell\u2013Derived Neurons in a Mouse Parkinson Disease Model","publication_year":2016,"publication_date":"2016-09-17","ids":{"openalex":"https://openalex.org/W2519967434","doi":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","mag":"2519967434","pmid":"https://pubmed.ncbi.nlm.nih.gov/27635972"},"language":"en","primary_location":{"id":"doi:10.1227/01.neu.0000499710.89208.c6","doi":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","is_oa":false,"landing_page_url":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","pdf_url":null,"source":{"id":"https://openalex.org/S111727011","display_name":"Neurosurgery","issn_l":"0148-396X","issn":["0148-396X","1081-1281","1524-4040"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neurosurgery","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5068981657","display_name":"Jonathan A. Lubin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jonathan A. Lubin","raw_affiliation_strings":["University of Wisconsin, Madison, Wisconsin"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Wisconsin, Madison, Wisconsin","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036576070","display_name":"Joslyn K. Strebe","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joslyn Strebe","raw_affiliation_strings":["University of Wisconsin, Madison, Wisconsin"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Wisconsin, Madison, Wisconsin","institution_ids":["https://openalex.org/I135310074"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5054371127","display_name":"John S. Kuo","orcid":"https://orcid.org/0000-0001-6809-4806","observed_orcids":["https://orcid.org/0000-0001-6809-4806"]},"institutions":[{"id":"https://openalex.org/I135310074","display_name":"University of Wisconsin\u2013Madison","ror":"https://ror.org/01y2jtd41","country_code":"US","type":"education","lineage":["https://openalex.org/I135310074"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John S. Kuo","raw_affiliation_strings":["University of Wisconsin, Madison, Wisconsin"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Wisconsin, Madison, Wisconsin","institution_ids":["https://openalex.org/I135310074"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I135310074"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.07026283,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"79","issue":"4","first_page":"N18","last_page":"N19"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.7973999977111816,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.7973999977111816,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":0.07980000227689743,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10919","display_name":"Neurological disorders and treatments","score":0.023099999874830246,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/parkinson-s-disease","display_name":"Parkinson's disease","score":0.9909999966621399},{"id":"https://openalex.org/keywords/midbrain-dopaminergic-neurons","display_name":"midbrain dopaminergic neurons","score":0.828000009059906},{"id":"https://openalex.org/keywords/human-induced-pluripotent-stem-cells","display_name":"human induced pluripotent stem cells","score":0.7480000257492065},{"id":"https://openalex.org/keywords/human-embryonic-stem-cells","display_name":"human embryonic stem cells","score":0.8360000252723694},{"id":"https://openalex.org/keywords/dreadd","display_name":"DREADD","score":0.8330000042915344},{"id":"https://openalex.org/keywords/clozapine-n-oxide","display_name":"clozapine-N-oxide","score":0.9290000200271606},{"id":"https://openalex.org/keywords/6-ohda-lesion","display_name":"6-hydroxydopamine lesion","score":0.8450000286102295},{"id":"https://openalex.org/keywords/crispr-gene-editing","display_name":"CRISPR gene editing","score":0.5429999828338623},{"id":"https://openalex.org/keywords/hm3dq","display_name":"hM3Dq","score":0.6800000071525574},{"id":"https://openalex.org/keywords/hm4di","display_name":"hM4Di","score":0.9879999756813049},{"id":"https://openalex.org/keywords/akinesia","display_name":"akinesia","score":0.6340000033378601},{"id":"https://openalex.org/keywords/motor-behavior","display_name":"motor behavior","score":0.35100001096725464}],"concepts":[{"id":"https://openalex.org/C107459253","wikidata":"https://www.wikidata.org/wiki/Q674925","display_name":"Induced pluripotent stem cell","level":4,"score":0.918951153755188},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8354060649871826},{"id":"https://openalex.org/C2779734285","wikidata":"https://www.wikidata.org/wiki/Q11085","display_name":"Parkinson's disease","level":3,"score":0.6394742131233215},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.628877580165863},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.6077868342399597},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.4909117817878723},{"id":"https://openalex.org/C145103041","wikidata":"https://www.wikidata.org/wiki/Q1151519","display_name":"Embryonic stem cell","level":3,"score":0.22114446759223938},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2139442265033722},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.19350850582122803},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09618237614631653},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0754173994064331},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07079923152923584}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002454","descriptor_name":"Cell Differentiation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004195","descriptor_name":"Disease Models, Animal","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009474","descriptor_name":"Neurons","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010300","descriptor_name":"Parkinson Disease","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D039904","descriptor_name":"Pluripotent Stem Cells","qualifier_ui":"Q000637","qualifier_name":"transplantation","is_major_topic":true},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1227/01.neu.0000499710.89208.c6","doi":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","is_oa":false,"landing_page_url":"https://doi.org/10.1227/01.neu.0000499710.89208.c6","pdf_url":null,"source":{"id":"https://openalex.org/S111727011","display_name":"Neurosurgery","issn_l":"0148-396X","issn":["0148-396X","1081-1281","1524-4040"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neurosurgery","raw_type":"journal-article"},{"id":"pmid:27635972","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/27635972","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Neurosurgery","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.98580002784729}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":5,"referenced_works":["https://openalex.org/W2097226043","https://openalex.org/W2106350754","https://openalex.org/W2231461486","https://openalex.org/W2342999003","https://openalex.org/W4234515672"],"related_works":["https://openalex.org/W2342999003","https://openalex.org/W4402452572","https://openalex.org/W7153235032","https://openalex.org/W4410023105","https://openalex.org/W4242774235","https://openalex.org/W3012192678","https://openalex.org/W7205046964","https://openalex.org/W2599153974","https://openalex.org/W3022482891","https://openalex.org/W2071001529"],"abstract_inverted_index":{"Parkinson":[0,452],"disease":[1,453],"(PD)":[2],"is":[3,60,88,121,603],"a":[4,204,210,425,448,542,622],"common":[5],"neurodegenerative":[6],"disorder":[7],"involving":[8],"the":[9,17,25,132,139,145,215,223,258,325,331,375,384,395,409,430,439,462,488,593],"loss":[10],"of":[11,126,147,183,197,201,264,280,307,333,352,427,451,471,481,499,511,536,545,595,610],"midbrain":[12],"dopaminergic":[13],"(mDA)":[14],"neurons":[15,41,87,105,233,277,474,502,540],"in":[16,24,29,44,66,141,189,214,291,374,383,447,490,541,568,579],"substantia":[18,216,327],"nigra,":[19,217],"with":[20,46,164,312,369,434,477,505,552,607],"diminished":[21],"dopamine":[22,64,82],"release":[23,65,83,120],"striatum.1,2":[26],"Rapid":[27],"progress":[28],"human":[30,156,239,241,472,500,538],"induced":[31,181,187],"pluripotent":[32],"stem":[33,158,618],"cell":[34,159,240,248],"(hPSC)":[35],"technology":[36,597],"may":[37],"generate":[38],"therapeutic":[39,96,566],"mDA":[40,86,104,142,175,191,232,265,295,353,443,473,501],"for":[42,56,94,320,429,588,614],"implantation":[43,351],"patients":[45,68],"PD.":[47],"Although":[48],"some":[49,67],"initial":[50],"clinical":[51,92,589,624],"trial":[52],"results":[53,420],"are":[54,583],"promising":[55],"this":[57,95,616],"approach,":[58],"it":[59],"likely":[61],"that":[62,106,253,422],"dysregulated":[63],"leads":[69],"to":[70,79,90,109,137,229,394,403,408,441,492,562,598],"no":[71,417],"symptom":[72],"improvement":[73,382],"or":[74],"uncontrollable":[75],"movements.3":[76],"The":[77,225],"ability":[78,440],"remotely":[80],"fine-tune":[81,442],"from":[84,274,324,521,554],"implanted":[85,221,254],"necessary":[89],"improve":[91],"efficacy":[93],"strategy.":[97],"Chen":[98,526],"et":[99,532],"al4":[100],"have":[101],"created":[102,163,208],"hPSC-derived":[103],"were":[107,162,220,227,272,310,338],"engineered":[108],"express":[110],"DREADDs":[111,140,169],"(designer":[112],"receptor":[113,133],"exclusively":[114],"activated":[115],"by":[116,123,234,363],"designer":[117],"drug).":[118],"Dopamine":[119],"regulated":[122],"exogenous":[124],"administration":[125,290,316,373,393,407],"an":[127,558],"otherwise":[128],"inert":[129],"small":[130],"molecule,":[131],"agonist":[134],"clozapine-N-oxide":[135,482],"(CNO),":[136],"activate":[138],"neurons.":[143,176,202],"With":[144],"use":[146,594],"CRISPR":[148,596],"(clustered":[149],"regularly":[150],"interspaced":[151],"short":[152],"palindromic":[153],"repeats)":[154],"technology,":[155],"embryonic":[157],"lines":[160],"(hESCs)":[161],"inhibitory":[165,190,576],"(hM4Di)":[166],"and":[167,171,243,284,313,330,346,388,467,475,478,495,503,506,519,564,575,585],"excitatory":[168,184,269,431,574],"(hM3Dq)":[170],"then":[172],"differentiated":[173],"into":[174,222,231,301,621],"By":[177],"patch-clamping":[178],"analysis,":[179],"CNO":[180,195,289,315,372,392,406,423,436,577],"depolarization":[182],"neuron":[185],"but":[186],"hyperpolarization":[188],"neurons,":[192,296,354],"suggesting":[193],"direct":[194],"regulation":[196],"these":[198],"2":[199,507],"types":[200],"In":[203,591],"mouse":[205,449,543],"PD":[206,308,569,625],"model":[207,450,544],"via":[209],"unilateral":[211,326],"6-hydroxydopamine\u2013induced":[212],"lesion":[213,329],"DREADD-expressing":[218,294],"hESCs":[219,226],"striatum.":[224],"confirmed":[228],"differentiate":[230],"stereologically":[235],"assessing":[236],"tyrosine":[237],"hydroxylase,":[238],"nuclei,":[242],"FOXA2":[244],"expression.":[245],"Human":[246],"neural":[247],"adhesion":[249],"molecule":[250],"staining":[251],"revealed":[252],"cells":[255],"successfully":[256],"innervate":[257],"caudate-putamen":[259],"(the":[260],"appropriate":[261],"projection":[262],"site":[263],"neurons).":[266],"Finally,":[267,304],"spontaneous":[268],"postsynaptic":[270],"currents":[271],"recorded":[273],"medium":[275],"spiny":[276],"(an":[278],"index":[279],"presynaptic":[281],"glutamate":[282],"release),":[283],"their":[285],"frequency":[286],"increased":[287],"after":[288,366,468,479,496,509],"hM3Dq":[292,376,432],"(excitatory)":[293,377],"indicating":[297],"successful":[298],"cellular":[299],"integration":[300],"host":[302],"circuitry.":[303],"motor":[305,336,360,381,400],"behaviors":[306],"mice":[309],"tested":[311],"without":[314],"(Figure).":[317],"To":[318],"test":[319,460,486],"limb":[321,344,386],"akinesia":[322],"resulting":[323],"nigra":[328],"effects":[332,578],"CNO,":[334],"multiple":[335],"tests":[337],"performed:":[339],"amphetamine-induced":[340,364],"rotation":[341,348,365,389],"test,":[342],"ipsilateral":[343,385,464],"touches,":[345],"CNO-induced":[347],"test.":[349],"After":[350],"all":[355],"groups":[356],"displayed":[357],"nearly":[358],"recovered":[359],"symptoms":[361,401,446],"assessed":[362],"4":[367],"months":[368],"overcompensation":[370],"thereafter.":[371],"group":[378,398,415,582],"caused":[379],"further":[380],"touches":[387,465],"tests,":[390],"whereas":[391],"hM4Di":[396],"(inhibitory)":[397],"showed":[399,416],"similar":[402],"pre-mDA":[404],"transplantation.":[405,572],"enhanced":[410,514],"green":[411,515],"fluorescent":[412,516],"protein":[413],"(control)":[414],"effect.":[418],"These":[419],"suggest":[421],"activates":[424],"gain":[426],"function":[428],"cells,":[433],"reversible":[435,584],"treatment":[437,476,504,581],"conferring":[438],"function.Figure:":[444],"Motor":[445],"can":[454],"be":[455],"reversibly":[456],"controlled.":[457],"A,":[458],"cylinder":[459],"shows":[461,487],"preferential":[463],"before":[466,494],"striatal":[469,497],"transplantation":[470,498],"withdrawal":[480,510],"(CNO).":[483],"B,":[484],"rotarod":[485],"changes":[489],"latency":[491],"fall":[493],"days":[508],"CNO.":[512],"EGFP,":[513],"protein.":[517],"Modified":[518],"reprinted":[520],"Cell":[522],"Stem":[523],"Cell,":[524],"18,":[525],"Y,":[527,531],"Xiong":[528],"M,":[529],"Dong":[530],"al.,":[533],"Chemical":[534],"control":[535,563],"grafted":[537],"PSC-derived":[539],"Parkinson's":[546],"disease,":[547],"pages":[548],"1-10,":[549],"Copyright":[550],"(2016),":[551],"permission":[553],"Elsevier.This":[555],"report":[556],"highlights":[557],"exogenous,":[559],"noninvasive":[560],"strategy":[561,620],"refine":[565],"outcomes":[567],"using":[570],"hPSC":[571],"Both":[573],"each":[580],"potentially":[586],"titrated":[587],"modulation.":[590],"addition,":[592],"introduce":[599],"transgenic":[600],"DREADD":[601],"expression":[602],"more":[604],"precise":[605],"compared":[606],"viral":[608],"transfection":[609],"hPSCs,":[611],"offering":[612],"hope":[613],"translating":[615],"novel":[617],"cell\u2013based":[619],"viable":[623],"therapy.":[626]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-09-23T00:00:00"}