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Progressive degeneration of human neural stem cells caused by pathogenic LRRK2
Open accessAbstract
Nuclear-architecture defects have been shown to correlate with the manifestation of a number of human diseases as well as ageing. It is therefore plausible that diseases whose manifestations correlate with ageing might be connected to the appearance of nuclear aberrations over time. We decided to evaluate nuclear organization in the context of ageing-associated disorders by focusing on a leucine-rich repeat kinase 2 (LRRK2) dominant mutation (G2019S; glycine-to-serine substitution at amino acid 2019), which is associated with familial and sporadic Parkinson's disease as well as impairment of adult neurogenesis in mice. Here we report on the generation of induced pluripotent stem cells (iPSCs) derived from Parkinson's disease patients and the implications of LRRK2(G2019S) mutation in human neural-stem-cell (NSC) populations. Mutant NSCs showed increased susceptibility to proteasomal stress as well as passage-dependent deficiencies in nuclear-envelope organization, clonal expansion and neuronal differentiation. Disease phenotypes were rescued by targeted correction of the LRRK2(G2019S) mutation with its wild-type counterpart in Parkinson's disease iPSCs and were recapitulated after targeted knock-in of the LRRK2(G2019S) mutation in human embryonic stem cells. Analysis of human brain tissue showed nuclear-envelope impairment in clinically diagnosed Parkinson's disease patients. Together, our results identify the nucleus as a previously unknown cellular organelle in Parkinson's disease pathology and may help to open new avenues for Parkinson's disease diagnoses as well as for the potential development of therapeutics targeting this fundamental cell structure.
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“we successfully generated homozygous WRN null ESC lines (ESCs-WRN−/−)”
From A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging (2015) · cites this paper as [10]
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Cites
Lamin A-dependent nuclear defects in human aging
Scaffidi, P., & Misteli, T. (2006) · Science · doi:10.1126/science.1127168 · Cited by 1,125
Dechat, T., Pfleghaar, K., Sengupta, K., Shimi, T., Shumaker, D. K., Solimando, L., & Goldman, R. D. (2008) · Genes & Development · doi:10.1101/gad.1652708 · Cited by 940
Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome
Liu, G.-H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S.-L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., et al. (2011) · Nature · doi:10.1038/nature09879 · Cited by 575
Self-citationThe role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease
Cookson, M. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2935 · Cited by 552
Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2
Deng, X., Dzamko, N. L., Prescott, A. R., Davies, P., Liu, Q., Yang, Q., Lee, J., Patricelli, M. P., Nomanbhoy, T. K., Alessi, D. R., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.538 · Cited by 434
Lamin B1 duplications cause autosomal dominant leukodystrophy
Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A. H., Hogan, K. J., Ptáček, L. J., & Fu, Y. (2006) · Nature Genetics · doi:10.1038/ng1872 · Cited by 407
Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression
Gehrke, S., Imai, Y., Sokol, N. S., & Lu, B. (2010) · Nature · doi:10.1038/nature09191 · Cited by 398
Nichols, R. J., Dzamko, N. L., Morrice, N. A., Campbell, D. G., Deák, M., Ordureau, A., Macartney, T., Tong, Y., Shen, J., Prescott, A. R., et al. (2010) · Biochemical Journal · doi:10.1042/bj20100483 · Cited by 390
Dzamko, N. L., Deák, M., Hentati, F., Reith, A. D., Prescott, A. R., Alessi, D. R., & Nichols, R. J. (2010) · Biochemical Journal · doi:10.1042/bj20100784 · Cited by 377
Li, W., Sun, W., Zhang, Y., Wei, W., Ambasudhan, R., Xia, P., Talantova, M. V., Lin, T., Kim, J., Wang, X., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014041108 · Cited by 376
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Tafaleng, E. N. (2015) · D-Scholarship@Pitt (University of Pittsburgh)
Aberrant cell retro-programming: A possible mechanism for neurodegeneration
Salama, M. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.02.003
Nivet, E., Liu, G., Montserrat, N., & Belmonte, J. C. I. (2013) · médecine/sciences · doi:10.1051/medsci/2013294006
Self-citationPathogenic LRRK2 mutations in nuclear ageing—A new organelle to study in Parkinson's disease
McKinley, J., McCarthy, A., & Lynch, T. (2013) · Movement Disorders · doi:10.1002/mds.25595
Neural stem cell degeneration in PD linked to nuclear defects
Malpass, K. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.230
Use of Induced Pluripotent Stem Cells in Aging Research
Isobe, K. (2015) · Springer eBooks · doi:10.1007/978-4-431-55763-0_4
Lu, B., Yao, Y., Sun, X., Cui, X., & Lu, B. (2013) · Protocol Exchange · doi:10.1038/protex.2013.085
Induced Pluripotent Stem Cells (iPSCs) to Study and Treat Movement Disorders
Datta, D., & Kim, K. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405195-9.00009-3
Stem cells in Parkinson’s disease: an updatePreprint
Gollamudi, S. (2016) · doi:10.15200/winn.148233.37308
Vilas, D. (2016) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
What if it was easier to prevent schizophrenia than to treat it?
Brennand, K. (2017) · Schizophrenia · doi:10.1038/s41537-017-0012-x
Robust Differentiation of Human Pluripotent Stem Cells to Skeletal Muscle Progenitors
Morrissey-Scoot, J. B. (2017) · TSpace (University of Toronto)
Eren, E., Erkan, E. P., Genç, Ş., & Genc, K. K. (2017) · Stem cells in clinical applications · doi:10.1007/978-3-319-59165-0_2
Cheung, A. Y. L. (2013) · TSpace (University of Toronto)
THE APPLICATIONS OF SYMPATHETIC SKIN RESPONSE IN CARPAL TUNNEL SYNDROME
Zaytseva, N. I., Белова, Н. В., Lagoda, D. Y., Yusupova, D. G., Korepina, O. S., Suponeva, N. A., Gnedovskaya, E. V., & Пирадов, М. А. (2017) · Siberian medical review · doi:10.20333/2500136-2017-4-58-65
Genome Editing and the Problem of Tetraploidy in Cell Modeling of the Genetic Form of Parkinsonism
Симонова, В. В., Vetchinova, A. S., Novosadova, E. V., Хаспеков, Л. Г., & Illarioshkin, S. N. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918090055
Neurochemical Aspects of Lewy Body Dementia
Farooqui, A. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816347-4.00004-0
Insulin resistance and Parkinson’s disease
Farooqui, A. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819603-8.00007-9
Neuronal identity and maturation
van den Hurk, M. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20161213mh
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Atkinson, S. P. (2020) · Stem Cells · doi:10.1002/stem.3195
Varderidou, S. (2022) · Utrecht University Repository (Utrecht University) · doi:10.33540/1458
Oun, A. (2022) · doi:10.33612/diss.253651629
None: Proteomic and functional comparison between human induced and embryonic stem cells
Brenes, A. J., Griesser, E., Sinclair, L. V., Davidson, L., Prescott, A. R., Singh, F., Hogg, E. K. J., Espejo-Serrano, C., Jiang, H., Yoshikawa, H., et al. (2024) · eLife · doi:10.7554/elife.92025.1.sa4
Author response: Proteomic and functional comparison between human induced and embryonic stem cells
Brenes, A. J., Griesser, E., Sinclair, L. V., Davidson, L., Prescott, A. R., Singh, F., Hogg, E. K. J., Espejo-Serrano, C., Jiang, H., Yoshikawa, H., et al. (2024) · eLife · doi:10.7554/elife.92025.2.sa0
Proteomic and functional comparison between human induced and embryonic stem cellsPreprint
Brenes, A. J., Griesser, E., Sinclair, L. V., Davidson, L., Prescott, A. R., Singh, F., Hogg, E. K. J., Espejo-Serrano, C., Jiang, H., Yoshikawa, H., et al. (2024) · eLife · doi:10.7554/elife.92025.2
Genome Editing and Human-Induced Pluripotent Stem Cells Facilitate Parkinson’s Disease Modeling
Polanco, C. M., Inzunza, J., Nalvarte, I., & Arias, J. (2025) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-031-94101-6_3
Stem Cell Therapy for Neurological Disorders: From Bench to Bedside
Barbuti, P. A. (2014) · Springer eBooks · doi:10.1007/978-81-322-2110-4_4
Wu, J., Ren, J., Cui, H., Xie, Y., & Tang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.25231192
Vorkapich, A., Mustafa, A., Flores, A., Zarbalis, K. S., & Giulivi, C. (2026) · Scientific Reports · doi:10.1038/s41598-026-43314-0
Lee, J. H., Han, J.-H., Jo, H. C., Jou, I., & Kim, D. Y. (2026) · Research Square · doi:10.21203/rs.3.rs-10289490/v1
Mann, L., Herrera-Rodriguez, R., van der Walt, F. E., Brimacombe, K. R., Sadouki, S., Misteli, T., Kubben, N., & Padeken, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.04.742751
Advances in hiPSC-Based Models of Complex Neurological Disorders
Giadone, R. M., Sartore, R., Arlotta, P., & Rubin, L. L. (2026) · Springer eBooks · doi:10.1007/978-3-032-31497-0_10
Burdman, G., Hanna, M., Yndart, A., Vashist, A., & Lakshmana, M. K. (2026) · Cells · doi:10.3390/cells15191768
Dopaminergic transmissive dormancy as a protective state against cellular stressPreprint
Zuurbier, K. R., Fonseca, R. S., Snowden, J., & Douglas, P. M. (2026) · Genes & Development · doi:10.1101/gad.353957.126
Meyer, A. K., Sampathkumar, C., Fransecky, L. R., Maisel, M., Kißenkötter, S., Weselek, G., Berndt, S., Kirsch, M., Schwarz, J., Hermann, A., et al. (2015) · Basal Ganglia · doi:10.1016/j.baga.2015.07.001
Metadata
- Authors
- Liu, G.-H., 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, R. D., Dubova, I., Thompson, J., III, J. Y., Esteban, C. R., Sancho-Martinez, I., & Belmonte, J. C. I.
- Affiliations
- Salk Institute for Biological Studies (US)
- Chinese Academy of Sciences (CN)
- University of California San Diego (US)
- Scripps Research Institute (US)
- Corresponding author
- Liu, Guang-Hui
- ORCID
- Venue
- Nature
- Published
- 2012-10-17
- Volume
- 491
- Issue
- 7425
- Pages
- 603-607
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3504651
- OpenAlex
- W2088778610
- Cited by
- 339
- References
- 31
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 19 · 2023: 14 · 2022: 24 · 2021: 15 · 2020: 38 · 2019: 28 · 2018: 21 · 2017: 27 · 2016: 36 · 2015: 28 · 2014: 28 · 2013: 34 · 2012: 6
- FWCI
- 19.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL AMU (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (P41GM103533)
- National Institute of Environmental Health Sciences (U01ES017166, ES017166)
- National Center for Research Resources (P41RR011823)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Parkinson's disease, LRRK2, G2019S mutation, neural stem cells, nuclear envelope, nuclear organization, induced pluripotent stem cells, clonal expansion, neuronal differentiation, human brain tissue
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Cell Differentiation, Cell Division, Cell Line, Clone Cells, Humans, Mutation, Nuclear Envelope, Parkinson Disease, Stress, Physiological, Apoptosis, Protein Serine-Threonine Kinases, Proteasome Endopeptidase Complex, Mutant Proteins, Embryonic Stem Cells, Gene Knock-In Techniques, Induced Pluripotent Stem Cells, Neural Stem Cells
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