Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases
| Autor(a) principal: | |
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| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://hdl.handle.net/1822/79269 |
Resumo: | Supplementary Information Te online version contains supplementary material available at https://doi.org/ 10.1038/s41598-022-16369-y. |
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Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseasesScience & TechnologySupplementary Information Te online version contains supplementary material available at https://doi.org/ 10.1038/s41598-022-16369-y.The establishment of robust human brain organoids to model cerebellar diseases is essential to study new therapeutic strategies for cerebellum-associated disorders. Machado-Joseph disease (MJD) is a cerebellar hereditary neurodegenerative disease, without therapeutic options able to prevent the disease progression. In the present work, control and MJD induced-pluripotent stem cells were used to establish human brain organoids. These organoids were characterized regarding brain development, cell type composition, and MJD-associated neuropathology markers, to evaluate their value for cerebellar diseases modeling. Our data indicate that the organoids recapitulated, to some extent, aspects of brain development, such as astroglia emerging after neurons and the presence of ventricular-like zones surrounded by glia and neurons that are found only in primate brains. Moreover, the brain organoids presented markers of neural progenitors proliferation, neuronal differentiation, inhibitory and excitatory synapses, and firing neurons. The established brain organoids also exhibited markers of cerebellar neurons progenitors and mature cerebellar neurons. Finally, MJD brain organoids showed higher ventricular-like zone numbers, an indication of lower maturation, and an increased number of ataxin-3-positive aggregates, compared with control organoids. Altogether, our data indicate that the established organoids recapitulate important characteristics of human brain development and exhibit cerebellar features, constituting a resourceful tool for testing therapeutic approaches for cerebellar diseases.This work was funded by the European Regional Development Fund (ERDF) through the Centro 2020 Regional Operational Programme under BrainHealth2020 projects (CENTRO-01-0145-FEDER-000008), through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under projects — UIDB/04539/2020 and UIDP/04539/2020, POCI-01-0145-FEDER-030737 (NeuroStemForMJD, PTDC/BTM-ORG/30737/2017), CEEC-IND/04242/2017, PhD Scholarships 2020.04751.BD and 2020.07385.BD. It was also funded by the National Ataxia Foundation, the French Muscular Dystrophy Association (AFM-Téléthon) Trampoline Grant #20126, EU Joint Programme—Neurodegenerative Disease Research (JPND) Project JPCO FUND/0005/2015-ModelPolyQ), and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund.info:eu-repo/semantics/publishedVersionNature ResearchUniversidade do MinhoBrás, JoãoHenriques, DanielMoreira, RicardoSantana, Magda M.Pedrosa, AnaAdão, DianaBraz, SandraÁlvaro, Ana Ritade Almeida, Luís PereiraMendonça, Liliana S.2022-07-222022-07-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/79269engBrás, J., Henriques, D., Moreira, R. et al. Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases. Sci Rep 12, 12513 (2022). https://doi.org/10.1038/s41598-022-16369-y2045-232210.1038/s41598-022-16369-y35869235https://www.nature.com/articles/s41598-022-16369-yinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:33:33Zoai:repositorium.sdum.uminho.pt:1822/79269Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:29:07.047063Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| title |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| spellingShingle |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases Brás, João Science & Technology |
| title_short |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| title_full |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| title_fullStr |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| title_full_unstemmed |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| title_sort |
Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases |
| author |
Brás, João |
| author_facet |
Brás, João Henriques, Daniel Moreira, Ricardo Santana, Magda M. Pedrosa, Ana Adão, Diana Braz, Sandra Álvaro, Ana Rita de Almeida, Luís Pereira Mendonça, Liliana S. |
| author_role |
author |
| author2 |
Henriques, Daniel Moreira, Ricardo Santana, Magda M. Pedrosa, Ana Adão, Diana Braz, Sandra Álvaro, Ana Rita de Almeida, Luís Pereira Mendonça, Liliana S. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
Brás, João Henriques, Daniel Moreira, Ricardo Santana, Magda M. Pedrosa, Ana Adão, Diana Braz, Sandra Álvaro, Ana Rita de Almeida, Luís Pereira Mendonça, Liliana S. |
| dc.subject.por.fl_str_mv |
Science & Technology |
| topic |
Science & Technology |
| description |
Supplementary Information Te online version contains supplementary material available at https://doi.org/ 10.1038/s41598-022-16369-y. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-07-22 2022-07-22T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/79269 |
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https://hdl.handle.net/1822/79269 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Brás, J., Henriques, D., Moreira, R. et al. Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases. Sci Rep 12, 12513 (2022). https://doi.org/10.1038/s41598-022-16369-y 2045-2322 10.1038/s41598-022-16369-y 35869235 https://www.nature.com/articles/s41598-022-16369-y |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Research |
| publisher.none.fl_str_mv |
Nature Research |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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