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dc.contributor.author장미윤-
dc.date.accessioned2021-11-12T02:25:51Z-
dc.date.available2021-11-12T02:25:51Z-
dc.date.issued2019-11-
dc.identifier.citationEMBO JOURNAL, v. 38, no. 24, article no. e101196en_US
dc.identifier.issn0261-4189-
dc.identifier.issn1460-2075-
dc.identifier.urihttps://www.embopress.org/doi/full/10.15252/embj.2018101196-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/166220-
dc.description.abstractParkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.en_US
dc.description.sponsorshipWe thank Dr. Beomseok Jeon [physician in charge of the patient described in this paper (HS Lee) in the Department of Neurology, Seoul National University Hospital] for descriptions of the patient's disease status. We thank the PETcore facility (Convergence Medicine Research Center, Asan Medical Center) for the technical support to acquire nanoScanPET/MRI images and analysis. This work was supported by grants from the Medical Research Center (2017R1A5A2015395), 2017M3A9B4062401, NRF-2017R1A2B2002220, and NRF-2016R1A2B4016342, funded by the National Research Foundation of Korea (NRF) of the Ministry of Science and ICT, Republic of Korea.en_US
dc.language.isoenen_US
dc.publisherWILEYen_US
dc.subjecthuman disease modelen_US
dc.subjecthuman pluripotent stem cellsen_US
dc.subjectLin28en_US
dc.subjectloss-of-function mutationen_US
dc.subjectParkinson’s diseaseen_US
dc.titleLIN28A loss of function is associated with Parkinson's disease pathogenesisen_US
dc.typeArticleen_US
dc.relation.volume38-
dc.identifier.doi10.15252/embj.2018101196-
dc.relation.page101196-101208-
dc.relation.journalEMBO JOURNAL-
dc.contributor.googleauthorChang, Mi-Yoon-
dc.contributor.googleauthorOh, Boram-
dc.contributor.googleauthorChoi, Jang-Eun-
dc.contributor.googleauthorSulistio, Yanuar Alan-
dc.contributor.googleauthorWoo, Hye-Ji-
dc.contributor.googleauthorJo, Ayoung-
dc.contributor.googleauthorKim, Jinil-
dc.contributor.googleauthorKim, Eun-Hee-
dc.contributor.googleauthorKim, Seung Won-
dc.contributor.googleauthorHwang, Jungwook-
dc.relation.code2019000502-
dc.sector.campusS-
dc.sector.daehakRESEARCH INSTITUTE[S]-
dc.sector.departmentHBRI-
dc.identifier.pidmychang-
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RESEARCH INSTITUTE[S](부설연구소) > ETC
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