Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.

Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present...

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Autores: Benetó N, Cozar M, Castilla-Vallmanya L, Zetterdahl OG, Sacultanu M, Segur-Bailach E, García-Morant M, Ribes A, Ahlenius H, Grinberg D, Vilageliu L, Canals I
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p17478
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17478
Access Level:acceso abierto
Palabra clave:astrocyte differentiation
induced pluripotent stem cells
lysosomal storage disorders
lysosomes
mucopolysaccharidosis III
neuronal differentiation
sanfilippo syndrome
siRNAs
substrate reduction therapy
transcription factor-based differentiation
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spelling Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.Benetó NCozar MCastilla-Vallmanya LZetterdahl OGSacultanu MSegur-Bailach EGarcía-Morant MRibes AAhlenius HGrinberg DVilageliu LCanals Iastrocyte differentiationinduced pluripotent stem cellslysosomal storage disorderslysosomesmucopolysaccharidosis IIIneuronal differentiationsanfilippo syndromesiRNAssubstrate reduction therapytranscription factor-based differentiationSanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated new neuronal and astrocytic models of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients' fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocytic models of Sanfilippo syndrome for future studies on disease mechanisms and drug development.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17478Journal of Clinical MedicineISSN: 20770383reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p174782026-05-27T12:37:41Z
dc.title.none.fl_str_mv Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
title Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
spellingShingle Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
Benetó N
astrocyte differentiation
induced pluripotent stem cells
lysosomal storage disorders
lysosomes
mucopolysaccharidosis III
neuronal differentiation
sanfilippo syndrome
siRNAs
substrate reduction therapy
transcription factor-based differentiation
title_short Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
title_full Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
title_fullStr Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
title_full_unstemmed Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
title_sort Neuronal and Astrocytic Differentiation from Sanfilippo C Syndrome iPSCs for Disease Modeling and Drug Development.
dc.creator.none.fl_str_mv Benetó N
Cozar M
Castilla-Vallmanya L
Zetterdahl OG
Sacultanu M
Segur-Bailach E
García-Morant M
Ribes A
Ahlenius H
Grinberg D
Vilageliu L
Canals I
author Benetó N
author_facet Benetó N
Cozar M
Castilla-Vallmanya L
Zetterdahl OG
Sacultanu M
Segur-Bailach E
García-Morant M
Ribes A
Ahlenius H
Grinberg D
Vilageliu L
Canals I
author_role author
author2 Cozar M
Castilla-Vallmanya L
Zetterdahl OG
Sacultanu M
Segur-Bailach E
García-Morant M
Ribes A
Ahlenius H
Grinberg D
Vilageliu L
Canals I
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv astrocyte differentiation
induced pluripotent stem cells
lysosomal storage disorders
lysosomes
mucopolysaccharidosis III
neuronal differentiation
sanfilippo syndrome
siRNAs
substrate reduction therapy
transcription factor-based differentiation
topic astrocyte differentiation
induced pluripotent stem cells
lysosomal storage disorders
lysosomes
mucopolysaccharidosis III
neuronal differentiation
sanfilippo syndrome
siRNAs
substrate reduction therapy
transcription factor-based differentiation
description Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated new neuronal and astrocytic models of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients' fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocytic models of Sanfilippo syndrome for future studies on disease mechanisms and drug development.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17478
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17478
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Journal of Clinical Medicine
ISSN: 20770383
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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