A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108913 https://doi.org/10.1038/srep34798 |
Resumo: | Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. |
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A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cellsAging, PrematureAlkaline PhosphataseCell DifferentiationChildGene Expression RegulationGuided Tissue RegenerationHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsIsotretinoinLamin Type AMesenchymal Stem CellsOsteogenesisProgeriaTretinoinHutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders.Springer Nature2016-10-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108913http://hdl.handle.net/10316/108913https://doi.org/10.1038/srep34798por2045-2322Lo Cicero, AlessandraJaskowiak, Anne-LaureEgesipe, Anne-LaureTournois, JohanaBrinon, BenjaminPitrez, Patrícia R.Ferreira, Linode Sandre-Giovannoli, AnnachiaraLévy, NicolasNissan, Xavierinfo: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:RCAAP2023-09-25T08:46:16Zoai:estudogeral.uc.pt:10316/108913Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:09.027965Repositório 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 |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
title |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
spellingShingle |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells Lo Cicero, Alessandra Aging, Premature Alkaline Phosphatase Cell Differentiation Child Gene Expression Regulation Guided Tissue Regeneration High-Throughput Screening Assays Humans Induced Pluripotent Stem Cells Isotretinoin Lamin Type A Mesenchymal Stem Cells Osteogenesis Progeria Tretinoin |
title_short |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
title_full |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
title_fullStr |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
title_full_unstemmed |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
title_sort |
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells |
author |
Lo Cicero, Alessandra |
author_facet |
Lo Cicero, Alessandra Jaskowiak, Anne-Laure Egesipe, Anne-Laure Tournois, Johana Brinon, Benjamin Pitrez, Patrícia R. Ferreira, Lino de Sandre-Giovannoli, Annachiara Lévy, Nicolas Nissan, Xavier |
author_role |
author |
author2 |
Jaskowiak, Anne-Laure Egesipe, Anne-Laure Tournois, Johana Brinon, Benjamin Pitrez, Patrícia R. Ferreira, Lino de Sandre-Giovannoli, Annachiara Lévy, Nicolas Nissan, Xavier |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Lo Cicero, Alessandra Jaskowiak, Anne-Laure Egesipe, Anne-Laure Tournois, Johana Brinon, Benjamin Pitrez, Patrícia R. Ferreira, Lino de Sandre-Giovannoli, Annachiara Lévy, Nicolas Nissan, Xavier |
dc.subject.por.fl_str_mv |
Aging, Premature Alkaline Phosphatase Cell Differentiation Child Gene Expression Regulation Guided Tissue Regeneration High-Throughput Screening Assays Humans Induced Pluripotent Stem Cells Isotretinoin Lamin Type A Mesenchymal Stem Cells Osteogenesis Progeria Tretinoin |
topic |
Aging, Premature Alkaline Phosphatase Cell Differentiation Child Gene Expression Regulation Guided Tissue Regeneration High-Throughput Screening Assays Humans Induced Pluripotent Stem Cells Isotretinoin Lamin Type A Mesenchymal Stem Cells Osteogenesis Progeria Tretinoin |
description |
Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-10-14 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108913 http://hdl.handle.net/10316/108913 https://doi.org/10.1038/srep34798 |
url |
http://hdl.handle.net/10316/108913 https://doi.org/10.1038/srep34798 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134134456549376 |