{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:51:10Z","timestamp":1790725870097,"version":"4.1.0"},"reference-count":40,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006691","name":"Harvard Medical School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008035","name":"Harvard Stem Cell Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006691","name":"Harvard Medical School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Stem Cell Reports"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1016\/j.stemcr.2019.12.005","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T10:42:45Z","timestamp":1577961765000},"page":"75-90","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":63,"title":["Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson's Disease Discovered Using Isogenic Human Dopaminergic Neurons"],"prefix":"10.1016","volume":"14","author":[{"given":"Tim","family":"Ahfeldt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alban","family":"Ordureau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Sarrafha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chicheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Piccinotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Grass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo M.","family":"Parfitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao A.","family":"Paulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiki","family":"Yanagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Uozumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasujiro","family":"Kiyota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Wade","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee L.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.stemcr.2019.12.005_bib1","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1242\/jcs.091181","article-title":"Lysosomal cell death at a glance","volume":"126","author":"Aits","year":"2013","journal-title":"J.\u00a0Cell Sci"},{"key":"10.1016\/j.stemcr.2019.12.005_bib2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nprot.2011.325","article-title":"Dynamic suspension culture for scalable expansion of undifferentiated human pluripotent stem cells","volume":"6","author":"Amit","year":"2011","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.stemcr.2019.12.005_bib3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fnana.2015.00091","article-title":"Oxidative stress and Parkinson's disease","volume":"9","author":"Blesa","year":"2015","journal-title":"Front Neuroanat."},{"key":"10.1016\/j.stemcr.2019.12.005_bib4","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1016\/j.febslet.2015.09.016","article-title":"Establishing diversity in the dopaminergic system","volume":"589","author":"Bodea","year":"2015","journal-title":"FEBS Lett."},{"key":"10.1016\/j.stemcr.2019.12.005_bib5","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1126\/science.aam9080","article-title":"Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease","volume":"357","author":"Burbulla","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.stemcr.2019.12.005_bib6","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1586\/ern.10.54","article-title":"Using 'omics' to define pathogenesis and biomarkers of Parkinson's disease","volume":"10","author":"Caudle","year":"2010","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.stemcr.2019.12.005_bib7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.2174\/1389202914666131210195808","article-title":"Genetic insights into sporadic Parkinson's disease pathogenesis","volume":"14","author":"Chai","year":"2013","journal-title":"Curr. Genomics"},{"key":"10.1016\/j.stemcr.2019.12.005_bib8","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2019.12.005_bib9","doi-asserted-by":"crossref","first-page":"141ra190","DOI":"10.1126\/scitranslmed.3003985","article-title":"Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease","volume":"4","author":"Cooper","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.stemcr.2019.12.005_bib10","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1056\/NEJMsr040330","article-title":"Derivation of embryonic stem-cell lines from human blastocysts","volume":"350","author":"Cowan","year":"2004","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2019.12.005_bib11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4103\/1673-5374.182692","article-title":"Induced pluripotent stem cells for modeling and cell therapy of Parkinson's disease","volume":"11","author":"Csobonyeiova","year":"2016","journal-title":"Neural Regen. Res."},{"key":"10.1016\/j.stemcr.2019.12.005_bib12","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson's disease: mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"10.1016\/j.stemcr.2019.12.005_bib13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson's disease","volume":"3","author":"Dias","year":"2013","journal-title":"J.\u00a0Parkinsons Dis."},{"key":"10.1016\/j.stemcr.2019.12.005_bib14","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/jmg.38.10.680","article-title":"Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36","volume":"38","author":"Hampshire","year":"2001","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.stemcr.2019.12.005_bib15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ncomms1669","article-title":"Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells","volume":"3","author":"Jiang","year":"2012","journal-title":"Nat. Commun."},{"key":"10.1016\/j.stemcr.2019.12.005_bib16","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1523\/JNEUROSCI.0984-06.2006","article-title":"Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled","volume":"26","author":"Keeney","year":"2006","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.stemcr.2019.12.005_bib17","doi-asserted-by":"crossref","first-page":"a008888","DOI":"10.1101\/cshperspect.a008888","article-title":"Genetics of Parkinson's disease","volume":"2","author":"Klein","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.stemcr.2019.12.005_bib18","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10648","article-title":"Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease","volume":"480","author":"Kriks","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2019.12.005_bib19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.devbrainres.2004.02.001","article-title":"Parkin expression in the developing mouse","volume":"149","author":"Kuhn","year":"2004","journal-title":"Brain Res. Dev. Brain Res."},{"key":"10.1016\/j.stemcr.2019.12.005_bib20","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/sctm.18-0088","article-title":"A comprehensive analysis of protocols for deriving dopaminergic neurons from human pluripotent stem cells","volume":"8","author":"Marton","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.stemcr.2019.12.005_bib21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.molcel.2018.03.012","article-title":"Dynamics of PARKIN-dependent mitochondrial Ubiquitylation in induced neurons and model systems revealed by Digital Snapshot proteomics","volume":"70","author":"Ordureau","year":"2018","journal-title":"Mol. Cell"},{"key":"10.1016\/j.stemcr.2019.12.005_bib22","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/mds.23221","article-title":"Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations","volume":"25","author":"Paisan-Ruiz","year":"2010","journal-title":"Mov. Disord."},{"key":"10.1016\/j.stemcr.2019.12.005_bib23","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fcell.2017.00110","article-title":"Crosstalk between lysosomes and mitochondria in Parkinson's disease","volume":"5","author":"Plotegher","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.stemcr.2019.12.005_bib24","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.stemcr.2019.12.005_bib25","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.cell.2016.04.032","article-title":"Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure","volume":"165","author":"Qian","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.005_bib26","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.stem.2013.01.008","article-title":"Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression","volume":"12","author":"Reinhardt","year":"2013","journal-title":"Cell stem cell"},{"key":"10.1016\/j.stemcr.2019.12.005_bib27","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.stemcr.2016.05.010","article-title":"Large-scale production of mature neurons from human pluripotent stem cells in a three-dimensional suspension culture system","volume":"6","author":"Rigamonti","year":"2016","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.stemcr.2019.12.005_bib28","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.cell.2013.11.009","article-title":"Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1alpha transcription","volume":"155","author":"Ryan","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.005_bib29","doi-asserted-by":"crossref","first-page":"e27495","DOI":"10.1371\/journal.pone.0027495","article-title":"Efficient culturing and genetic manipulation of human pluripotent stem cells","volume":"6","author":"Schinzel","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.stemcr.2019.12.005_bib30","first-page":"67","article-title":"Genetic basis of Parkinson's disease: inheritance, penetrance, and expression","volume":"4","author":"Schulte","year":"2011","journal-title":"Appl. Clin. Genet."},{"key":"10.1016\/j.stemcr.2019.12.005_bib31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.stemcr.2015.02.019","article-title":"Mitochondrial alterations by PARKIN in dopaminergic neurons using PARK2 patient-specific and PARK2 knockout isogenic iPSC lines","volume":"4","author":"Shaltouki","year":"2015","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.stemcr.2019.12.005_bib32","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/nbt1037","article-title":"Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein","volume":"22","author":"Shaner","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2019.12.005_bib33","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1152\/jn.00317.2005","article-title":"Slow oscillatory firing: a major firing pattern\u00a0of\u00a0dopamine neurons in the ventral tegmental area","volume":"94","author":"Shi","year":"2005","journal-title":"J.\u00a0Neurophysiol."},{"key":"10.1016\/j.stemcr.2019.12.005_bib34","doi-asserted-by":"crossref","first-page":"55863","DOI":"10.18632\/oncotarget.10150","article-title":"Cytoplasmic vacuolization in cell death and survival","volume":"7","author":"Shubin","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.stemcr.2019.12.005_bib35","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0092-8674(01)00603-1","article-title":"Dual inhibition of sister chromatid separation at metaphase","volume":"107","author":"Stemmann","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.005_bib36","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.stemcr.2018.09.006","article-title":"T-type calcium channels determine the vulnerability of dopaminergic neurons to mitochondrial stress in familial Parkinson disease","volume":"11","author":"Tabata","year":"2018","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.stemcr.2019.12.005_bib37","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nrn2499","article-title":"Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction","volume":"9","author":"Tai","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.stemcr.2019.12.005_bib38","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1093\/hmg\/ddm159","article-title":"Parkinson's disease","volume":"16 Spec No. 2","author":"Thomas","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.stemcr.2019.12.005_bib39","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1212\/WNL.35.8.1215","article-title":"Parkinson's disease: loss of neurons from the ventral tegmental area contralateral to therapeutic surgical lesions","volume":"35","author":"Uhl","year":"1985","journal-title":"Neurology"},{"key":"10.1016\/j.stemcr.2019.12.005_bib40","doi-asserted-by":"crossref","first-page":"20270","DOI":"10.1038\/srep20270","article-title":"Transcriptional comparison of human induced and primary midbrain dopaminergic neurons","volume":"6","author":"Xia","year":"2016","journal-title":"Sci. Rep."}],"container-title":["Stem Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119304448?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119304448?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:42:34Z","timestamp":1761990154000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213671119304448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["S2213671119304448"],"URL":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.12.005","relation":{},"ISSN":["2213-6711"],"issn-type":[{"value":"2213-6711","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson's Disease Discovered Using Isogenic Human Dopaminergic Neurons","name":"articletitle","label":"Article Title"},{"value":"Stem Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.12.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}