Stem cell models of Angelman syndrome
Angelman syndrome (AS) is an imprinted neurodevelopmental disorder that lacks a cure, characterized by developmental delay, intellectual impairment, seizures, ataxia, and paroxysmal laughter. The condition arises due to the loss of the maternally inherited copy of the UBE3A gene in neurons. The pate...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1274040/full |
| _version_ | 1827789743411167232 |
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| author | João Camões dos Santos João Camões dos Santos Carolina Appleton Carolina Appleton Carolina Appleton Francisca Cazaux Mateus Francisca Cazaux Mateus Rita Covas Rita Covas Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Simão Teixeira da Rocha Simão Teixeira da Rocha |
| author_facet | João Camões dos Santos João Camões dos Santos Carolina Appleton Carolina Appleton Carolina Appleton Francisca Cazaux Mateus Francisca Cazaux Mateus Rita Covas Rita Covas Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Simão Teixeira da Rocha Simão Teixeira da Rocha |
| author_sort | João Camões dos Santos |
| collection | DOAJ |
| description | Angelman syndrome (AS) is an imprinted neurodevelopmental disorder that lacks a cure, characterized by developmental delay, intellectual impairment, seizures, ataxia, and paroxysmal laughter. The condition arises due to the loss of the maternally inherited copy of the UBE3A gene in neurons. The paternally inherited UBE3A allele is unable to compensate because it is silenced by the expression of an antisense transcript (UBE3A-ATS) on the paternal chromosome. UBE3A, encoding enigmatic E3 ubiquitin ligase variants, regulates target proteins by either modifying their properties/functions or leading them to degradation through the proteasome. Over time, animal models, particularly the Ube3amat−/pat+ Knock-Out (KO) mice, have significantly contributed to our understanding of the molecular mechanisms underlying AS. However, a shift toward human pluripotent stem cell models (PSCs), such as human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), has gained momentum. These stem cell models accurately capture human genetic and cellular characteristics, offering an alternative or a complement to animal experimentation. Human stem cells possess the remarkable ability to recapitulate neurogenesis and generate “brain-in-a-dish” models, making them valuable tools for studying neurodevelopmental disorders like AS. In this review, we provide an overview of the current state-of-the-art human stem cell models of AS and explore their potential to become the preclinical models of choice for drug screening and development, thus propelling AS therapeutic advancements and improving the lives of affected individuals. |
| first_indexed | 2024-03-11T17:24:03Z |
| format | Article |
| id | doaj.art-c0745e5a535e429a9295d07e6a7900e4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-11T17:24:03Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c0745e5a535e429a9295d07e6a7900e42023-10-19T07:10:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-10-011110.3389/fcell.2023.12740401274040Stem cell models of Angelman syndromeJoão Camões dos Santos0João Camões dos Santos1Carolina Appleton2Carolina Appleton3Carolina Appleton4Francisca Cazaux Mateus5Francisca Cazaux Mateus6Rita Covas7Rita Covas8Evguenia Pavlovna Bekman9Evguenia Pavlovna Bekman10Evguenia Pavlovna Bekman11Simão Teixeira da Rocha12Simão Teixeira da Rocha13iBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalDepartment of Animal Biology, Faculdade de Ciências da Universidade de Lisboa, Lisbon, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalThe Egas Moniz Center for Interdisciplinary Research (CiiEM), Caparica, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAssociate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, PortugalAngelman syndrome (AS) is an imprinted neurodevelopmental disorder that lacks a cure, characterized by developmental delay, intellectual impairment, seizures, ataxia, and paroxysmal laughter. The condition arises due to the loss of the maternally inherited copy of the UBE3A gene in neurons. The paternally inherited UBE3A allele is unable to compensate because it is silenced by the expression of an antisense transcript (UBE3A-ATS) on the paternal chromosome. UBE3A, encoding enigmatic E3 ubiquitin ligase variants, regulates target proteins by either modifying their properties/functions or leading them to degradation through the proteasome. Over time, animal models, particularly the Ube3amat−/pat+ Knock-Out (KO) mice, have significantly contributed to our understanding of the molecular mechanisms underlying AS. However, a shift toward human pluripotent stem cell models (PSCs), such as human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), has gained momentum. These stem cell models accurately capture human genetic and cellular characteristics, offering an alternative or a complement to animal experimentation. Human stem cells possess the remarkable ability to recapitulate neurogenesis and generate “brain-in-a-dish” models, making them valuable tools for studying neurodevelopmental disorders like AS. In this review, we provide an overview of the current state-of-the-art human stem cell models of AS and explore their potential to become the preclinical models of choice for drug screening and development, thus propelling AS therapeutic advancements and improving the lives of affected individuals.https://www.frontiersin.org/articles/10.3389/fcell.2023.1274040/fullAngelman syndrome (AS)genomic imprintingUBE3Apluripotent stem cells (PSCs)disease modelingbrain organoids |
| spellingShingle | João Camões dos Santos João Camões dos Santos Carolina Appleton Carolina Appleton Carolina Appleton Francisca Cazaux Mateus Francisca Cazaux Mateus Rita Covas Rita Covas Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Evguenia Pavlovna Bekman Simão Teixeira da Rocha Simão Teixeira da Rocha Stem cell models of Angelman syndrome Frontiers in Cell and Developmental Biology Angelman syndrome (AS) genomic imprinting UBE3A pluripotent stem cells (PSCs) disease modeling brain organoids |
| title | Stem cell models of Angelman syndrome |
| title_full | Stem cell models of Angelman syndrome |
| title_fullStr | Stem cell models of Angelman syndrome |
| title_full_unstemmed | Stem cell models of Angelman syndrome |
| title_short | Stem cell models of Angelman syndrome |
| title_sort | stem cell models of angelman syndrome |
| topic | Angelman syndrome (AS) genomic imprinting UBE3A pluripotent stem cells (PSCs) disease modeling brain organoids |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1274040/full |
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