Stem cell models of Angelman syndrome

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

João Camões dos Santos¹  Simão Teixeira da Rocha¹  Rita Covas¹  Francisca Cazaux Mateus¹  Carolina Appleton²  Evguenia Pavlovna Bekman³ 

[1] iBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Associate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;iBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Associate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Department of Animal Biology, Faculdade de Ciências da Universidade de Lisboa, Lisbon, Portugal;iBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;Associate Laboratory i4HB Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal;The Egas Moniz Center for Interdisciplinary Research (CiiEM), Caparica, Portugal;

关键词: Angelman syndrome (AS);    genomic imprinting;    UBE3A;    pluripotent stem cells (PSCs);    disease modeling;    brain organoids;    antisense oligonucleotides (ASOs);   

DOI  :  10.3389/fcell.2023.1274040

 received in 2023-08-07, accepted in 2023-10-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Camões dos Santos, Appleton, Cazaux Mateus, Covas, Bekman and da Rocha.