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

Author:

Astorkia Maider,Lachman Herbert M.,Zheng DeyouORCID

Abstract

AbstractAutism 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.

Publisher

Cold Spring Harbor Laboratory

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3