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Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction / Arquimedes CHEFFER in Molecular Autism, 11 (2020)
[article]
Titre : Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction Type de document : Texte imprimé et/ou numérique Auteurs : Arquimedes CHEFFER, Auteur ; Lea Jessica FLITSCH, Auteur ; Tamara KRUTENKO, Auteur ; Pascal RÖDERER, Auteur ; Liubov SOKHRANYAEVA, Auteur ; Vira IEFREMOVA, Auteur ; Mohamad HAJO, Auteur ; Michael PEITZ, Auteur ; Martin Karl SCHWARZ, Auteur ; Oliver BRÜSTLE, Auteur Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Brain organoids Cell reprogramming In vitro differentiation Induced pluripotent stem cells Neuronal connectivity Index. décimale : PER Périodiques Résumé : The controlled differentiation of pluripotent stem cells (PSCs) into neurons and glia offers a unique opportunity to study early stages of human central nervous system development under controlled conditions in vitro. With the advent of cell reprogramming and the possibility to generate induced pluripotent stem cells (iPSCs) from any individual in a scalable manner, these studies can be extended to a disease- and patient-specific level. Autism spectrum disorder (ASD) is considered a neurodevelopmental disorder, with substantial evidence pointing to early alterations in neurogenesis and network formation as key pathogenic drivers. For that reason, ASD represents an ideal candidate for stem cell-based disease modeling. Here, we provide a concise review on recent advances in the field of human iPSC-based modeling of syndromic and non-syndromic forms of ASD, with a particular focus on studies addressing neuronal dysfunction and altered connectivity. We further discuss recent efforts to translate stem cell-based disease modeling to 3D via brain organoid and cell transplantation approaches, which enable the investigation of disease mechanisms in a tissue-like context. Finally, we describe advanced tools facilitating the assessment of altered neuronal function, comment on the relevance of iPSC-based models for the assessment of pharmaceutical therapies and outline potential future routes in stem cell-based ASD research. En ligne : http://dx.doi.org/10.1186/s13229-020-00383-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438
in Molecular Autism > 11 (2020)[article] Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction [Texte imprimé et/ou numérique] / Arquimedes CHEFFER, Auteur ; Lea Jessica FLITSCH, Auteur ; Tamara KRUTENKO, Auteur ; Pascal RÖDERER, Auteur ; Liubov SOKHRANYAEVA, Auteur ; Vira IEFREMOVA, Auteur ; Mohamad HAJO, Auteur ; Michael PEITZ, Auteur ; Martin Karl SCHWARZ, Auteur ; Oliver BRÜSTLE, Auteur.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020)
Mots-clés : Autism spectrum disorder Brain organoids Cell reprogramming In vitro differentiation Induced pluripotent stem cells Neuronal connectivity Index. décimale : PER Périodiques Résumé : The controlled differentiation of pluripotent stem cells (PSCs) into neurons and glia offers a unique opportunity to study early stages of human central nervous system development under controlled conditions in vitro. With the advent of cell reprogramming and the possibility to generate induced pluripotent stem cells (iPSCs) from any individual in a scalable manner, these studies can be extended to a disease- and patient-specific level. Autism spectrum disorder (ASD) is considered a neurodevelopmental disorder, with substantial evidence pointing to early alterations in neurogenesis and network formation as key pathogenic drivers. For that reason, ASD represents an ideal candidate for stem cell-based disease modeling. Here, we provide a concise review on recent advances in the field of human iPSC-based modeling of syndromic and non-syndromic forms of ASD, with a particular focus on studies addressing neuronal dysfunction and altered connectivity. We further discuss recent efforts to translate stem cell-based disease modeling to 3D via brain organoid and cell transplantation approaches, which enable the investigation of disease mechanisms in a tissue-like context. Finally, we describe advanced tools facilitating the assessment of altered neuronal function, comment on the relevance of iPSC-based models for the assessment of pharmaceutical therapies and outline potential future routes in stem cell-based ASD research. En ligne : http://dx.doi.org/10.1186/s13229-020-00383-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex / Wardiya AFSHAR SABER in Molecular Autism, 11 (2020)
[article]
Titre : Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex Type de document : Texte imprimé et/ou numérique Auteurs : Wardiya AFSHAR SABER, Auteur ; Mustafa SAHIN, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Mots-clés : Astrocytes Autism Brain organoids CRISPR/Cas9 Cortical tuber Human pluripotent stem cells Neurons Purkinje neurons Tuberous sclerosis complex Therapeutics, and Quadrant Biosciences and has served on the Scientific Advisory Board of Sage Therapeutics, Roche, Takeda, and PTEN Research Foundation. Index. décimale : PER Périodiques Résumé : Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/Cas9 offers the advantage of preserving patient-specific genetic background and the ability to generate isogenic controls by correcting a specific mutation. The patient cell line and the isogenic control can be differentiated into the cell type of interest to model various aspects of TSC. In this review, we discuss the remarkable capacity of these cells to be used as a model for TSC in two- and three-dimensional cultures, the potential variability in iPSC models, and highlight differences between findings reported to date. En ligne : http://dx.doi.org/10.1186/s13229-020-0320-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Molecular Autism > 11 (2020) . - 16 p.[article] Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex [Texte imprimé et/ou numérique] / Wardiya AFSHAR SABER, Auteur ; Mustafa SAHIN, Auteur . - 16 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 16 p.
Mots-clés : Astrocytes Autism Brain organoids CRISPR/Cas9 Cortical tuber Human pluripotent stem cells Neurons Purkinje neurons Tuberous sclerosis complex Therapeutics, and Quadrant Biosciences and has served on the Scientific Advisory Board of Sage Therapeutics, Roche, Takeda, and PTEN Research Foundation. Index. décimale : PER Périodiques Résumé : Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/Cas9 offers the advantage of preserving patient-specific genetic background and the ability to generate isogenic controls by correcting a specific mutation. The patient cell line and the isogenic control can be differentiated into the cell type of interest to model various aspects of TSC. In this review, we discuss the remarkable capacity of these cells to be used as a model for TSC in two- and three-dimensional cultures, the potential variability in iPSC models, and highlight differences between findings reported to date. En ligne : http://dx.doi.org/10.1186/s13229-020-0320-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology / Cristina CHERONI in Molecular Autism, 11 (2020)
[article]
Titre : Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology Type de document : Texte imprimé et/ou numérique Auteurs : Cristina CHERONI, Auteur ; Nicolò CAPORALE, Auteur ; Giuseppe TESTA, Auteur Article en page(s) : 69 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Brain organoids Developmental neurotoxicology Endocrine disruptors Gene × environment Neurodevelopmental disorders Pluripotent stem cells Index. décimale : PER Périodiques Résumé : The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals' genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment. En ligne : http://dx.doi.org/10.1186/s13229-020-00370-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433
in Molecular Autism > 11 (2020) . - 69 p.[article] Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology [Texte imprimé et/ou numérique] / Cristina CHERONI, Auteur ; Nicolò CAPORALE, Auteur ; Giuseppe TESTA, Auteur . - 69 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 69 p.
Mots-clés : Autism spectrum disorder Brain organoids Developmental neurotoxicology Endocrine disruptors Gene × environment Neurodevelopmental disorders Pluripotent stem cells Index. décimale : PER Périodiques Résumé : The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals' genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment. En ligne : http://dx.doi.org/10.1186/s13229-020-00370-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433