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Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes

Maider Astorkia, Herbert M. Lachman, View ORCID ProfileDeyou Zheng
doi: https://doi.org/10.1101/2021.10.15.464577
Maider Astorkia
1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
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Herbert M. Lachman
2Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY, USA
3Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA
4Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
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Deyou Zheng
1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
3Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA
4Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
5Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA
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  • ORCID record for Deyou Zheng
  • For correspondence: deyou.zheng@einsteinmed.org
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Abstract

Autism spectrum disorder is a neurodevelopmental disorder, affecting 1-2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits. Recent application of single cell technologies, especially single cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single cell data provides opportunities for multi-level computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls. Our results indicate that at a global level there are cell-cell communication differences in autism in comparison to controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of change is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibit increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways are differentially expressed, but genes in the pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks. Overall, our proof-of-principle computational study using single cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type affects can be valuable for understanding autism pathogenesis.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 15, 2021.
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Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes
Maider Astorkia, Herbert M. Lachman, Deyou Zheng
bioRxiv 2021.10.15.464577; doi: https://doi.org/10.1101/2021.10.15.464577
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Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes
Maider Astorkia, Herbert M. Lachman, Deyou Zheng
bioRxiv 2021.10.15.464577; doi: https://doi.org/10.1101/2021.10.15.464577

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