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
-
Résultat de la recherche
13 recherche sur le mot-clé 'Transcriptome'
Affiner la recherche Générer le flux rss de la recherche
Partager le résultat de cette recherche Faire une suggestion
Hierarchical cortical transcriptome disorganization in autism / M. V. LOMBARDO in Molecular Autism, 8 (2017)
[article]
Titre : Hierarchical cortical transcriptome disorganization in autism Type de document : Texte imprimé et/ou numérique Auteurs : M. V. LOMBARDO, Auteur ; E. COURCHESNE, Auteur ; N. E. LEWIS, Auteur ; T. PRAMPARO, Auteur Article en page(s) : 29p. Langues : Anglais (eng) Mots-clés : Autism Gene co-expression networks Immune Synapse Systems biology Transcriptome Translation Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. METHODS: Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. RESULTS: We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. CONCLUSIONS: These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation. En ligne : http://dx.doi.org/10.1186/s13229-017-0147-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330
in Molecular Autism > 8 (2017) . - 29p.[article] Hierarchical cortical transcriptome disorganization in autism [Texte imprimé et/ou numérique] / M. V. LOMBARDO, Auteur ; E. COURCHESNE, Auteur ; N. E. LEWIS, Auteur ; T. PRAMPARO, Auteur . - 29p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 29p.
Mots-clés : Autism Gene co-expression networks Immune Synapse Systems biology Transcriptome Translation Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. METHODS: Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. RESULTS: We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. CONCLUSIONS: These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation. En ligne : http://dx.doi.org/10.1186/s13229-017-0147-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder / T. SAELIW in Molecular Autism, 9 (2018)
[article]
Titre : Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : T. SAELIW, Auteur ; C. TANGSUWANSRI, Auteur ; S. THONGKORN, Auteur ; W. CHONCHAIYA, Auteur ; K. SUPHAPEETIPORN, Auteur ; A. MUTIRANGURA, Auteur ; T. TENCOMNAO, Auteur ; V. W. HU, Auteur ; T. SARACHANA, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Alu Elements Autism Spectrum Disorder/genetics Case-Control Studies Cells, Cultured DNA Methylation Epigenesis, Genetic Female Gene Regulatory Networks Genome, Human Humans Male Transcriptome Autism spectrum disorder Epigenetic regulation Gene expression profiles Lymphoblastoid cell lines Neuroinflammation Retrotransposon Sex bias Subgrouping Index. décimale : PER Périodiques Résumé : Background: Alu elements are a group of repetitive elements that can influence gene expression through CpG residues and transcription factor binding. Altered gene expression and methylation profiles have been reported in various tissues and cell lines from individuals with autism spectrum disorder (ASD). However, the role of Alu elements in ASD remains unclear. We thus investigated whether Alu elements are associated with altered gene expression profiles in ASD. Methods: We obtained five blood-based gene expression profiles from the Gene Expression Omnibus database and human Alu-inserted gene lists from the TranspoGene database. Differentially expressed genes (DEGs) in ASD were identified from each study and overlapped with the human Alu-inserted genes. The biological functions and networks of Alu-inserted DEGs were then predicted by Ingenuity Pathway Analysis (IPA). A combined bisulfite restriction analysis of lymphoblastoid cell lines (LCLs) derived from 36 ASD and 20 sex- and age-matched unaffected individuals was performed to assess the global DNA methylation levels within Alu elements, and the Alu expression levels were determined by quantitative RT-PCR. Results: In ASD blood or blood-derived cells, 320 Alu-inserted genes were reproducibly differentially expressed. Biological function and pathway analysis showed that these genes were significantly associated with neurodevelopmental disorders and neurological functions involved in ASD etiology. Interestingly, estrogen receptor and androgen signaling pathways implicated in the sex bias of ASD, as well as IL-6 signaling and neuroinflammation signaling pathways, were also highlighted. Alu methylation was not significantly different between the ASD and sex- and age-matched control groups. However, significantly altered Alu methylation patterns were observed in ASD cases sub-grouped based on Autism Diagnostic Interview-Revised scores compared with matched controls. Quantitative RT-PCR analysis of Alu expression also showed significant differences between ASD subgroups. Interestingly, Alu expression was correlated with methylation status in one phenotypic ASD subgroup. Conclusion: Alu methylation and expression were altered in LCLs from ASD subgroups. Our findings highlight the association of Alu elements with gene dysregulation in ASD blood samples and warrant further investigation. Moreover, the classification of ASD individuals into subgroups based on phenotypes may be beneficial and could provide insights into the still unknown etiology and the underlying mechanisms of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0213-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 27p.[article] Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder [Texte imprimé et/ou numérique] / T. SAELIW, Auteur ; C. TANGSUWANSRI, Auteur ; S. THONGKORN, Auteur ; W. CHONCHAIYA, Auteur ; K. SUPHAPEETIPORN, Auteur ; A. MUTIRANGURA, Auteur ; T. TENCOMNAO, Auteur ; V. W. HU, Auteur ; T. SARACHANA, Auteur . - 27p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 27p.
Mots-clés : Alu Elements Autism Spectrum Disorder/genetics Case-Control Studies Cells, Cultured DNA Methylation Epigenesis, Genetic Female Gene Regulatory Networks Genome, Human Humans Male Transcriptome Autism spectrum disorder Epigenetic regulation Gene expression profiles Lymphoblastoid cell lines Neuroinflammation Retrotransposon Sex bias Subgrouping Index. décimale : PER Périodiques Résumé : Background: Alu elements are a group of repetitive elements that can influence gene expression through CpG residues and transcription factor binding. Altered gene expression and methylation profiles have been reported in various tissues and cell lines from individuals with autism spectrum disorder (ASD). However, the role of Alu elements in ASD remains unclear. We thus investigated whether Alu elements are associated with altered gene expression profiles in ASD. Methods: We obtained five blood-based gene expression profiles from the Gene Expression Omnibus database and human Alu-inserted gene lists from the TranspoGene database. Differentially expressed genes (DEGs) in ASD were identified from each study and overlapped with the human Alu-inserted genes. The biological functions and networks of Alu-inserted DEGs were then predicted by Ingenuity Pathway Analysis (IPA). A combined bisulfite restriction analysis of lymphoblastoid cell lines (LCLs) derived from 36 ASD and 20 sex- and age-matched unaffected individuals was performed to assess the global DNA methylation levels within Alu elements, and the Alu expression levels were determined by quantitative RT-PCR. Results: In ASD blood or blood-derived cells, 320 Alu-inserted genes were reproducibly differentially expressed. Biological function and pathway analysis showed that these genes were significantly associated with neurodevelopmental disorders and neurological functions involved in ASD etiology. Interestingly, estrogen receptor and androgen signaling pathways implicated in the sex bias of ASD, as well as IL-6 signaling and neuroinflammation signaling pathways, were also highlighted. Alu methylation was not significantly different between the ASD and sex- and age-matched control groups. However, significantly altered Alu methylation patterns were observed in ASD cases sub-grouped based on Autism Diagnostic Interview-Revised scores compared with matched controls. Quantitative RT-PCR analysis of Alu expression also showed significant differences between ASD subgroups. Interestingly, Alu expression was correlated with methylation status in one phenotypic ASD subgroup. Conclusion: Alu methylation and expression were altered in LCLs from ASD subgroups. Our findings highlight the association of Alu elements with gene dysregulation in ASD blood samples and warrant further investigation. Moreover, the classification of ASD individuals into subgroups based on phenotypes may be beneficial and could provide insights into the still unknown etiology and the underlying mechanisms of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0213-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism / Weicheng DUAN in Autism Research, 13-3 (March 2020)
[article]
Titre : Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism Type de document : Texte imprimé et/ou numérique Auteurs : Weicheng DUAN, Auteur ; Kang WANG, Auteur ; Yijie DUAN, Auteur ; Xufeng CHU, Auteur ; Ruoyun MA, Auteur ; Ping HU, Auteur ; Bo XIONG, Auteur Article en page(s) : p.352-368 Langues : Anglais (eng) Mots-clés : PPI network autism gene regulation integrated analysis synaptic transmission transcriptome Index. décimale : PER Périodiques Résumé : Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA-Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein-protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex-Adult subgroup, Gria1 in the Cortex-Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus-Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352-368. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Abnormal transcriptional regulation accounts for a significant portion of Autism Spectrum Disorder. In this study, we performed transcriptome analyses of mouse models to identify common downstream targets of transcriptional regulators involved in ASD. We identified several recurrent target genes that are close related to the common pathological process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRM2, NRXN1, GRIN3A, ITGAM, GRIN2A, GABRA2, and CAMK4. These results provide potentially important targets for understanding the molecular mechanism of ASD. En ligne : http://dx.doi.org/10.1002/aur.2240 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421
in Autism Research > 13-3 (March 2020) . - p.352-368[article] Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism [Texte imprimé et/ou numérique] / Weicheng DUAN, Auteur ; Kang WANG, Auteur ; Yijie DUAN, Auteur ; Xufeng CHU, Auteur ; Ruoyun MA, Auteur ; Ping HU, Auteur ; Bo XIONG, Auteur . - p.352-368.
Langues : Anglais (eng)
in Autism Research > 13-3 (March 2020) . - p.352-368
Mots-clés : PPI network autism gene regulation integrated analysis synaptic transmission transcriptome Index. décimale : PER Périodiques Résumé : Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA-Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein-protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex-Adult subgroup, Gria1 in the Cortex-Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus-Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352-368. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Abnormal transcriptional regulation accounts for a significant portion of Autism Spectrum Disorder. In this study, we performed transcriptome analyses of mouse models to identify common downstream targets of transcriptional regulators involved in ASD. We identified several recurrent target genes that are close related to the common pathological process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRM2, NRXN1, GRIN3A, ITGAM, GRIN2A, GABRA2, and CAMK4. These results provide potentially important targets for understanding the molecular mechanism of ASD. En ligne : http://dx.doi.org/10.1002/aur.2240 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment / Yihui ZHU in Autism Research, 14-1 (January 2021)
[article]
Titre : Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment Type de document : Texte imprimé et/ou numérique Auteurs : Yihui ZHU, Auteur ; Charles E. MORDAUNT, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; Marie A. CAUDILL, Auteur ; Olga V. MALYSHEVA, Auteur ; Joshua W. MILLER, Auteur ; Ralph GREEN, Auteur ; S. Jill JAMES, Auteur ; Stepan B. MELNYK, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Rebecca J. SCHMIDT, Auteur ; Janine M. LASALLE, Auteur Article en page(s) : p.11-28 Langues : Anglais (eng) Mots-clés : autism spectrum disorder maternal blood neurodevelopment nutrition one-carbon metabolites prenatal transcriptome Index. décimale : PER Périodiques Résumé : The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients. En ligne : http://dx.doi.org/10.1002/aur.2428 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441
in Autism Research > 14-1 (January 2021) . - p.11-28[article] Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment [Texte imprimé et/ou numérique] / Yihui ZHU, Auteur ; Charles E. MORDAUNT, Auteur ; Blythe DURBIN-JOHNSON, Auteur ; Marie A. CAUDILL, Auteur ; Olga V. MALYSHEVA, Auteur ; Joshua W. MILLER, Auteur ; Ralph GREEN, Auteur ; S. Jill JAMES, Auteur ; Stepan B. MELNYK, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Rebecca J. SCHMIDT, Auteur ; Janine M. LASALLE, Auteur . - p.11-28.
Langues : Anglais (eng)
in Autism Research > 14-1 (January 2021) . - p.11-28
Mots-clés : autism spectrum disorder maternal blood neurodevelopment nutrition one-carbon metabolites prenatal transcriptome Index. décimale : PER Périodiques Résumé : The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients. En ligne : http://dx.doi.org/10.1002/aur.2428 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441 Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells / S. AVAZZADEH in Molecular Autism, 10 (2019)
[article]
Titre : Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells Type de document : Texte imprimé et/ou numérique Auteurs : S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Autism Calcium signaling Induced pluripotent stem cells NRXN1alpha Neurons Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414
in Molecular Autism > 10 (2019) . - 52 p.[article] Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells [Texte imprimé et/ou numérique] / S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur . - 52 p.
Langues : Anglais (eng)
in Molecular Autism > 10 (2019) . - 52 p.
Mots-clés : Autism Calcium signaling Induced pluripotent stem cells NRXN1alpha Neurons Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome / N. L. PACHECO in Molecular Autism, 8 (2017)
PermalinkRole of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders / L. S. NGUYEN in Molecular Autism, 9 (2018)
PermalinkStrong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex / M. SCHWEDE in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)
PermalinkTranscriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy / Cuixia FAN in Molecular Autism, 11 (2020)
PermalinkProfiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology / L. S. NGUYEN in Molecular Autism, 7 (2016)
Permalink