Mutations in GFAP alter early lineage commitment of organoids

22 p.-7 fig.

Detalhes bibliográficos
Autores: Dykstra, Werner, Matusova, Zuzana, Rachel A., Battaglia, Abaffy, Pavel, Goya-Iglesias, Nuria, Pérez-Sala, Dolores, Ahlenius, Henrik, Kubista, Mikael, Pasterkamp, R. Jeroen, Li, Li, Chao, Jianfei, Shi, Yanhong, Valihrach, Lukas, Pekny, Milos, Hol, E.M.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/396857
Acesso em linha:http://hdl.handle.net/10261/396857
Access Level:acceso abierto
Palavra-chave:Alexander disease
GFAP
iPSCsNeural organoids
Lineage commitment
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network_name_str España
repository_id_str
spelling Mutations in GFAP alter early lineage commitment of organoidsDykstra, WernerMatusova, ZuzanaRachel A., BattagliaAbaffy, PavelGoya-Iglesias, NuriaPérez-Sala, DoloresAhlenius, HenrikKubista, MikaelPasterkamp, R. JeroenLi, LiChao, JianfeiShi, YanhongValihrach, LukasPekny, MilosHol, E.M.Alexander diseaseGFAPiPSCsNeural organoidsLineage commitment22 p.-7 fig.Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in the developing brain. Here, we used AxD patient- derived induced pluripotent stem cells (iPSCs) to explore the impact of mutant GFAP during neurodifferentiation. Our results show that GFAP is already expressed in iPSCs. Moreover, we have found that mutations in GFAP can severely affect neural organoid development through altering lineage commitment in embryoid bodies. Together, these results support the notion that GFAP plays a role as an early modulator of neurodevelopment.This work was supported by ‘la Caixa’ Foundation, LCF/PR/HR21/52410002; European Joint Programme on Rare Diseases (EJP RD 2019 ALEXANDER); ZonMW 463002004 Svenska Sällskapet för Medicinsk Forskning, FO02021- 0082, FO2022-1032; Vetenskapsrådet, 2018- 02695, 2020- 01148,2019- 00284; Söderberg's Foundations; ALF Gothenburg, 146051, 965939; Petrus och Augusta Hedlunds Stiftelse, M-2019-1026, M2018- 0803; Czech science foundation, 24-11364S, 24-12028S; Institute of Biotechnology of the Czech Academy of Sciences (IBT CAS) institutional support (RVO 86652036); Amlöv's Foundation; Agencia Estatal de Investigación, 10.13039/501100011033, MICIN and ERDF PID2021-126827OB-I00, RTI2018- 097624-B-I00; Comunidad Autónoma de Madrid PIPF-2022/SAL- GL-25771.Peer reviewedJohn Wiley & SonsFundación la CaixaEuropean Joint Programme on Rare DiseasesSwedish Society for Medical ResearchSwedish Research CouncilRagnar Söderberg FoundationAnna Lindh FoundationPetrus and Augusta Hedlund FoundationAcademy of Sciences of the Czech RepublicRune and Ulla Amlöv Foundation for Neurological and Rheumatological ResearchAgencia Estatal de Investigación (España)Comunidad de MadridDykstra, Werner [0000-0002-7663-4689]Matusova, Zuzana [0000-0002-5014-5801]Rachel A., Battaglia [0000-0003-3187-6964]Abaffy, Pavel [0000-0002-7571-8880]Goya-Iglesias, Nuria [0009-0003-5830-1287]Pérez-Sala, Dolores [0000-0003-0600-665X]Ahlenius, Henrik [0000-0001-8958-6148]Kubista, Mikael [0000-0002-2940-352X]Pasterkamp, R. Jeroen [0000-0003-1631-6440]Li, Li [0000-0001-7886-6056]Chao, Jianfei [0000-0003-4607-9925]Shi, Yanhong [0000-0002-3938-5839]Valihrach, Lukas [0000-0002-6704-4337]Pekny, Milos [0000-0003-1607-8075]Hol, E.M. [0000-0001-5604-2603]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/396857reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126827OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-097624-B-I00https://doi.org/10.1002/glia.70049Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3968572026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mutations in GFAP alter early lineage commitment of organoids
title Mutations in GFAP alter early lineage commitment of organoids
spellingShingle Mutations in GFAP alter early lineage commitment of organoids
Dykstra, Werner
Alexander disease
GFAP
iPSCsNeural organoids
Lineage commitment
title_short Mutations in GFAP alter early lineage commitment of organoids
title_full Mutations in GFAP alter early lineage commitment of organoids
title_fullStr Mutations in GFAP alter early lineage commitment of organoids
title_full_unstemmed Mutations in GFAP alter early lineage commitment of organoids
title_sort Mutations in GFAP alter early lineage commitment of organoids
dc.creator.none.fl_str_mv Dykstra, Werner
Matusova, Zuzana
Rachel A., Battaglia
Abaffy, Pavel
Goya-Iglesias, Nuria
Pérez-Sala, Dolores
Ahlenius, Henrik
Kubista, Mikael
Pasterkamp, R. Jeroen
Li, Li
Chao, Jianfei
Shi, Yanhong
Valihrach, Lukas
Pekny, Milos
Hol, E.M.
author Dykstra, Werner
author_facet Dykstra, Werner
Matusova, Zuzana
Rachel A., Battaglia
Abaffy, Pavel
Goya-Iglesias, Nuria
Pérez-Sala, Dolores
Ahlenius, Henrik
Kubista, Mikael
Pasterkamp, R. Jeroen
Li, Li
Chao, Jianfei
Shi, Yanhong
Valihrach, Lukas
Pekny, Milos
Hol, E.M.
author_role author
author2 Matusova, Zuzana
Rachel A., Battaglia
Abaffy, Pavel
Goya-Iglesias, Nuria
Pérez-Sala, Dolores
Ahlenius, Henrik
Kubista, Mikael
Pasterkamp, R. Jeroen
Li, Li
Chao, Jianfei
Shi, Yanhong
Valihrach, Lukas
Pekny, Milos
Hol, E.M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación la Caixa
European Joint Programme on Rare Diseases
Swedish Society for Medical Research
Swedish Research Council
Ragnar Söderberg Foundation
Anna Lindh Foundation
Petrus and Augusta Hedlund Foundation
Academy of Sciences of the Czech Republic
Rune and Ulla Amlöv Foundation for Neurological and Rheumatological Research
Agencia Estatal de Investigación (España)
Comunidad de Madrid
Dykstra, Werner [0000-0002-7663-4689]
Matusova, Zuzana [0000-0002-5014-5801]
Rachel A., Battaglia [0000-0003-3187-6964]
Abaffy, Pavel [0000-0002-7571-8880]
Goya-Iglesias, Nuria [0009-0003-5830-1287]
Pérez-Sala, Dolores [0000-0003-0600-665X]
Ahlenius, Henrik [0000-0001-8958-6148]
Kubista, Mikael [0000-0002-2940-352X]
Pasterkamp, R. Jeroen [0000-0003-1631-6440]
Li, Li [0000-0001-7886-6056]
Chao, Jianfei [0000-0003-4607-9925]
Shi, Yanhong [0000-0002-3938-5839]
Valihrach, Lukas [0000-0002-6704-4337]
Pekny, Milos [0000-0003-1607-8075]
Hol, E.M. [0000-0001-5604-2603]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alexander disease
GFAP
iPSCsNeural organoids
Lineage commitment
topic Alexander disease
GFAP
iPSCsNeural organoids
Lineage commitment
description 22 p.-7 fig.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/396857
url http://hdl.handle.net/10261/396857
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126827OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-097624-B-I00
https://doi.org/10.1002/glia.70049
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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