Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Détail de l'auteur
Auteur Derek J. C. TAI |
Documents disponibles écrits par cet auteur (1)
Faire une suggestion Affiner la recherche
Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons / Catarina M. SEABRA in Molecular Autism, 11 (2020)
[article]
Titre : Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons Type de document : Texte imprimé et/ou numérique Auteurs : Catarina M. SEABRA, Auteur ; Tatsiana ANEICHYK, Auteur ; Serkan ERDIN, Auteur ; Derek J. C. TAI, Auteur ; Celine E. F. DE ESCH, Auteur ; Parisa RAZAZ, Auteur ; Yu AN, Auteur ; Poornima MANAVALAN, Auteur ; Ashok RAGAVENDRAN, Auteur ; Alexei STORTCHEVOI, Auteur ; Clemer ABAD, Auteur ; Juan I. YOUNG, Auteur ; Patricia MACIEL, Auteur ; Michael E. TALKOWSKI, Auteur ; James F. GUSELLA, Auteur Article en page(s) : 45 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Crispr Mbd5 Mouse Ndd Neurons Transcriptomics Index. décimale : PER Périodiques Résumé : BACKGROUND: MBD5, encoding the methyl-CpG-binding domain 5 protein, has been proposed as a necessary and sufficient driver of the 2q23.1 microdeletion syndrome. De novo missense and protein-truncating variants from exome sequencing studies have directly implicated MBD5 in the etiology of autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs). However, little is known concerning the specific function(s) of MBD5. METHODS: To gain insight into the complex interactions associated with alteration of MBD5 in individuals with ASD and related NDDs, we explored the transcriptional landscape of MBD5 haploinsufficiency across multiple mouse brain regions of a heterozygous hypomorphic Mbd5(+/GT) mouse model, and compared these results to CRISPR-mediated mutations of MBD5 in human iPSC-derived neuronal models. RESULTS: Gene expression analyses across three brain regions from Mbd5(+/GT) mice showed subtle transcriptional changes, with cortex displaying the most widespread changes following Mbd5 reduction, indicating context-dependent effects. Comparison with MBD5 reduction in human neuronal cells reinforced the context-dependence of gene expression changes due to MBD5 deficiency. Gene co-expression network analyses revealed gene clusters that were associated with reduced MBD5 expression and enriched for terms related to ciliary function. LIMITATIONS: These analyses included a limited number of mouse brain regions and neuronal models, and the effects of the gene knockdown are subtle. As such, these results will not reflect the full extent of MBD5 disruption across human brain regions during early neurodevelopment in ASD, or capture the diverse spectrum of cell-type-specific changes associated with MBD5 alterations. CONCLUSIONS: Our study points to modest and context-dependent transcriptional consequences of Mbd5 disruption in the brain. It also suggests a possible link between MBD5 and perturbations in ciliary function, which is an established pathogenic mechanism in developmental disorders and syndromes. En ligne : http://dx.doi.org/10.1186/s13229-020-00354-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Molecular Autism > 11 (2020) . - 45 p.[article] Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons [Texte imprimé et/ou numérique] / Catarina M. SEABRA, Auteur ; Tatsiana ANEICHYK, Auteur ; Serkan ERDIN, Auteur ; Derek J. C. TAI, Auteur ; Celine E. F. DE ESCH, Auteur ; Parisa RAZAZ, Auteur ; Yu AN, Auteur ; Poornima MANAVALAN, Auteur ; Ashok RAGAVENDRAN, Auteur ; Alexei STORTCHEVOI, Auteur ; Clemer ABAD, Auteur ; Juan I. YOUNG, Auteur ; Patricia MACIEL, Auteur ; Michael E. TALKOWSKI, Auteur ; James F. GUSELLA, Auteur . - 45 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 45 p.
Mots-clés : Autism spectrum disorder Crispr Mbd5 Mouse Ndd Neurons Transcriptomics Index. décimale : PER Périodiques Résumé : BACKGROUND: MBD5, encoding the methyl-CpG-binding domain 5 protein, has been proposed as a necessary and sufficient driver of the 2q23.1 microdeletion syndrome. De novo missense and protein-truncating variants from exome sequencing studies have directly implicated MBD5 in the etiology of autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs). However, little is known concerning the specific function(s) of MBD5. METHODS: To gain insight into the complex interactions associated with alteration of MBD5 in individuals with ASD and related NDDs, we explored the transcriptional landscape of MBD5 haploinsufficiency across multiple mouse brain regions of a heterozygous hypomorphic Mbd5(+/GT) mouse model, and compared these results to CRISPR-mediated mutations of MBD5 in human iPSC-derived neuronal models. RESULTS: Gene expression analyses across three brain regions from Mbd5(+/GT) mice showed subtle transcriptional changes, with cortex displaying the most widespread changes following Mbd5 reduction, indicating context-dependent effects. Comparison with MBD5 reduction in human neuronal cells reinforced the context-dependence of gene expression changes due to MBD5 deficiency. Gene co-expression network analyses revealed gene clusters that were associated with reduced MBD5 expression and enriched for terms related to ciliary function. LIMITATIONS: These analyses included a limited number of mouse brain regions and neuronal models, and the effects of the gene knockdown are subtle. As such, these results will not reflect the full extent of MBD5 disruption across human brain regions during early neurodevelopment in ASD, or capture the diverse spectrum of cell-type-specific changes associated with MBD5 alterations. CONCLUSIONS: Our study points to modest and context-dependent transcriptional consequences of Mbd5 disruption in the brain. It also suggests a possible link between MBD5 and perturbations in ciliary function, which is an established pathogenic mechanism in developmental disorders and syndromes. En ligne : http://dx.doi.org/10.1186/s13229-020-00354-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427