Characterization of cell-cell communication in autistic brains with single-cell transcriptomes

Astorkia, Maider; Lachman, Herbert M.; Zheng, Deyou

doi:10.1186/s11689-022-09441-1

Cited by 7 publications

(6 citation statements)

References 121 publications

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“…To explore how the dysregulated genes are related to autism and other neural disorder risk, we compared the cell type specific DEGs to gene sets associated with brain disorders ( Figure 6 ), including genes associated with ASD, schizophrenia (SZ), bipolar disorder, intellectual disability (ID), and attention deficit hyperactivity disorder (ADHD) 41 . Most of the cell types showed an enrichment of genes in the ASD_SFARI, ASD_AUTISMKB, ADHD and BIPOLAR databases, while only Cortical_neurons (C18 and C6) showed an enrichment in genes associated with Schizophrenia (SZ_GWAS).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to studying cell population changes and cell type specific effects, scRNA-seq data are also valuable for investigating cell-cell communications across different cell types 41 . We thus applied CellChat 45 and identified 12,763 ligand-receptor (L-R) interactions in the two iPS control samples and a slightly fewer interactions in in the CHD8 KO samples (11,490) ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

“…In the first, EnrichGO function from clusterProfiler 40 was used to identify overrepresented GO terms in “biological processes,” with simplify function used to reduce redundancy. In the second, we tested the overrepresentation of our DEGs in gene sets associated with ASD, schizophrenia (SCZ), intellectual Disability (ID), Attention Deficit Hyperactivity Disorder (ADHD), and neurodevelopmental disorders, for a total of seven gene sets curated in our previous work 41 . Fisher test was applied using GeneOverlap 42 package.…”

Section: Methodsmentioning

confidence: 99%

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Molecular and network disruptions in neurodevelopment uncovered by single cell transcriptomics analysis ofCHD8heterozygous cerebral organoids

Astorkia,

Liu,

Pedrosa

et al. 2023

Preprint

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About 100 genes have been associated with significantly increased risks of autism spectrum disorders (ASD) with an estimate of ∼1000 genes that may be involved. The new challenge now is to investigate the molecular and cellular functions of these genes during neural and brain development, and then even more challenging, to link the altered molecular and cellular phenotypes to the ASD clinical manifestations. In this study, we use single cell RNA-seq analysis to study one of the top risk gene,CHD8, in cerebral organoids, which models early neural development. We identify 21 cell clusters in the organoid samples, representing non-neuronal cells, neural progenitors, and early differentiating neurons at the start of neural cell fate commitment. Comparisons of the cells with one copy of theCHD8knockout and their isogenic controls uncover thousands of differentially expressed genes, which are enriched with function related to neural and brain development, with genes and pathways previously implicated in ASD, but surprisingly not for Schizophrenia and intellectual disability risk genes. The comparisons also find cell composition changes, indicating potential altered neural differential trajectories uponCHD8reduction. Moreover, we find that cell-cell communications are affected in theCHD8knockout organoids, including the interactions between neural and glial cells. Taken together, our results provide new data for understanding CHD8 functions in the early stages of neural lineage development and interaction.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular and network disruptions in neurodevelopment uncovered by single cell transcriptomics analysis ofCHD8heterozygous cerebral organoids

Astorkia,

Liu,

Pedrosa

et al. 2023

Preprint

Self Cite

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“…The development of ASD is closely related with neuron–neuron communications ( 64 ). Synaptic adhesion molecules mediate the communications between presynaptic and postsynaptic neurons and play critical roles in synapse development and plasticity ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders

Zhang

Hou²,

Ou³

et al. 2022

Front. Endocrinol.

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The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2–MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.

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“…ASD neuroimaging research examines the brain from a variety of perspectives including brain structure, functional connections, and neurometabolic [ 8 – 10 ]. Structural magnetic resonance imaging (sMRI) is a technique for examining the anatomical structure of the brain.…”

Section: Introductionmentioning

confidence: 99%

Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on Autism Spectrum Disorder Neuroimaging

Lü

Zhang

et al. 2022

Disease Markers

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Background. Autism spectrum disorder (ASD) is a chronic developmental disability caused by differences in the brain. The gold standard for the diagnosis of this condition is based on behavioral science, but research on the application of neurological detection to diagnose the atypical nervous system of ASD is ongoing. ASD neuroimaging research involves the examination of the brain’s structure, functional connections, and neurometabolic. However, limited medical resource and the unique heterogeneity of ASD have resulted in many challenges when neuroimaging is utilized. Objective. This bibliometric study is aimed at summarizing themes and trends in research on autism spectrum disorder neuroimaging and at proposing potential directions for future inquiry. Methods. Citations were downloaded from the Web of Science Core Collection database on neuroimaging published from January 1, 2012, to December 31, 2021. The retrieved information was analyzed using Bibliometric.com, CiteSpace.5.8. R3, and VOS viewer. Results. A total of 1,363 papers were published across 58 regions. The United States was the leading source of publications. The League of European Research Universities published the largest number of articles (171). Burst keywords from 2018 to 2021 include identification and network. The clusters of references that continued into 2020 included graph theory, functional connectivity, and classification, which represent key research topics. Conclusions. Imaging data is being used to identify neuro-network models with higher accuracy for ASD discrimination. Functional near-infrared imaging is advantageous compared to other neuroimaging. In the future, research on systematic and accurate computer-aided diagnosis technology should be encouraged. Moreover, the study of neuroimaging of ASD in different psychological and behavioral states can inspire new ideas about the diagnosis and intervention training of ASD and should be explored.

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Characterization of cell-cell communication in autistic brains with single-cell transcriptomes

Cited by 7 publications

References 121 publications

Molecular and network disruptions in neurodevelopment uncovered by single cell transcriptomics analysis ofCHD8heterozygous cerebral organoids

Molecular and network disruptions in neurodevelopment uncovered by single cell transcriptomics analysis ofCHD8heterozygous cerebral organoids

Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders

Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on Autism Spectrum Disorder Neuroimaging

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