Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia

16 p.-7 fig. 1 graph. abst.

Detalles Bibliográficos
Autores: Canals, Isaac, Comella Bolla, Andrea, Cepeda-Prado, E., Avaliani, Natalia, Crowe, James A., Oburoglu, Leal, Bruzelius, Andreas, King, Naomi, Pajares, María Ángeles, Pérez-Sala, Dolores, Heuer, Andreas, Rylander Ottosson, Daniella, Soriano, Jordi, Ahlenius, Henrik
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/309652
Acceso en línea:http://hdl.handle.net/10261/309652
Access Level:acceso abierto
Palabra clave:Human pluripotent stem cells
CRISPR/Cas9 genome editing
Frontotemporal dementia
Electrophysiology
Neuronal network analysis
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spelling Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementiaCanals, IsaacComella Bolla, AndreaCepeda-Prado, E.Avaliani, NataliaCrowe, James A.Oburoglu, LealBruzelius, AndreasKing, NaomiPajares, María ÁngelesPérez-Sala, DoloresHeuer, AndreasRylander Ottosson, DaniellaSoriano, JordiAhlenius, HenrikHuman pluripotent stem cellsCRISPR/Cas9 genome editingFrontotemporal dementiaElectrophysiologyNeuronal network analysis16 p.-7 fig. 1 graph. abst.Frontotemporal dementia is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro Frontotemporal dementia disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of Frontotemporal dementia astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development.This study was supported by funding from the Swedish Society for Medical Research (SSMF, S20-0003), Kockska, Segerfalk and Hardebo foundations to IC; the Swedish Research Council (VR:2018-02695), Swedish Alzheimer and Åhlen foundations to HA; the Swedish Research Council (VR:2016-01789) to AH; and the Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (RTI2018-097624-BI00) and European Regional Development Fund to DPS.Peer reviewedOxford University PressSwedish Society for Medical ResearchSwedish Research CouncilSwedish Alzheimer FoundationAgencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)European CommissionCanals, Isaac [0000-0002-2689-268X]Comella Bolla, Andrea [0000-0001-9480-5050]Cepeda-Prado, E. [0000-0001-9781-3742]Avaliani, Natalia [0000-0002-2986-1520]Crowe, James A. [0000-0003-4487-9048]Oburoglu, Leal [0000-0003-0130-6602]Bruzelius, Andreas [0000-0002-7175-3590]Pajares, María A. [0000-0002-4714-9051]Pérez-Sala, Dolores [0000-0003-0600-665X]Heuer, Andreas [0000-0003-0300-7606]Rylander Ottosson, Daniella [0000-0002-9270-3576]Soriano, Jordi [0000-0003-2676-815X]Ahlenius, Henrik [0000-0001-8958-6148]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/309652reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1093/braincomms/fcad158Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3096522026-05-22T06:33:51Z
dc.title.none.fl_str_mv Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
title Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
spellingShingle Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
Canals, Isaac
Human pluripotent stem cells
CRISPR/Cas9 genome editing
Frontotemporal dementia
Electrophysiology
Neuronal network analysis
title_short Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
title_full Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
title_fullStr Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
title_full_unstemmed Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
title_sort Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
dc.creator.none.fl_str_mv Canals, Isaac
Comella Bolla, Andrea
Cepeda-Prado, E.
Avaliani, Natalia
Crowe, James A.
Oburoglu, Leal
Bruzelius, Andreas
King, Naomi
Pajares, María Ángeles
Pérez-Sala, Dolores
Heuer, Andreas
Rylander Ottosson, Daniella
Soriano, Jordi
Ahlenius, Henrik
author Canals, Isaac
author_facet Canals, Isaac
Comella Bolla, Andrea
Cepeda-Prado, E.
Avaliani, Natalia
Crowe, James A.
Oburoglu, Leal
Bruzelius, Andreas
King, Naomi
Pajares, María Ángeles
Pérez-Sala, Dolores
Heuer, Andreas
Rylander Ottosson, Daniella
Soriano, Jordi
Ahlenius, Henrik
author_role author
author2 Comella Bolla, Andrea
Cepeda-Prado, E.
Avaliani, Natalia
Crowe, James A.
Oburoglu, Leal
Bruzelius, Andreas
King, Naomi
Pajares, María Ángeles
Pérez-Sala, Dolores
Heuer, Andreas
Rylander Ottosson, Daniella
Soriano, Jordi
Ahlenius, Henrik
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Swedish Society for Medical Research
Swedish Research Council
Swedish Alzheimer Foundation
Agencia Estatal de Investigación (España)
Ministerio de Ciencia e Innovación (España)
European Commission
Canals, Isaac [0000-0002-2689-268X]
Comella Bolla, Andrea [0000-0001-9480-5050]
Cepeda-Prado, E. [0000-0001-9781-3742]
Avaliani, Natalia [0000-0002-2986-1520]
Crowe, James A. [0000-0003-4487-9048]
Oburoglu, Leal [0000-0003-0130-6602]
Bruzelius, Andreas [0000-0002-7175-3590]
Pajares, María A. [0000-0002-4714-9051]
Pérez-Sala, Dolores [0000-0003-0600-665X]
Heuer, Andreas [0000-0003-0300-7606]
Rylander Ottosson, Daniella [0000-0002-9270-3576]
Soriano, Jordi [0000-0003-2676-815X]
Ahlenius, Henrik [0000-0001-8958-6148]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Human pluripotent stem cells
CRISPR/Cas9 genome editing
Frontotemporal dementia
Electrophysiology
Neuronal network analysis
topic Human pluripotent stem cells
CRISPR/Cas9 genome editing
Frontotemporal dementia
Electrophysiology
Neuronal network analysis
description 16 p.-7 fig. 1 graph. abst.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
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/10261/309652
url http://hdl.handle.net/10261/309652
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1093/braincomms/fcad158
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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 15.811543

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