Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism cortex but did not address their cell-type specificity. Moreover, it is unknown whether there is a core of genes dysregulated across multiple neocortical regions. We applied RNA sequencing to postmortem brain tissue samples from autism patients and neurologically normal controls and combined our data with previously published datasets. We then identified genes, pathways, and alternative splicing events which are dysregulated in five neocortical regions in autism. To gain information about cell-type specificity of the dysregulated genes, we analyzed single-nuclei RNA sequencing data of adult human cortex and intersected cell-type-specific gene signatures with genes dysregulated in autism in specific cortical regions. We found that autism-associated gene expression changes across 4 frontal and temporal cortex regions converge on 27 genes related to immune response and enriched in human astrocytes, microglia, and brain endothelium. Shared splicing changes, however, are found in genes predominantly associated with synaptic function and adult interneurons and projection neurons. Finally, we demonstrate that regions of DNA differentially methylated in autism overlap genes associated with development and enriched in human cortical oligodendrocytes. Our study identifies signatures of autism molecular pathology shared across neocortical regions, as well as neural cell types enriched for common dysregulated genes, thus paving way for assessing cell-type-specific mechanisms of autism pathology.
October 15, 2020
Identifying biopsychosocial factors that impact decompressive laminectomy outcomes in veterans with lumbar spinal stenosis: a prospective cohort study.
September 17, 2020
Sports activity patterns and cardio-metabolic health over time among adults in Germany: Results of a nationwide 12-year follow-up study.
August 3, 2020
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.
- ENDO: 2020ENDO 2020 Annual Conference has been canceled due to COVID-19. Here are highlights of emerging data that has still been released. Keep an eye out for ENDO Online 2020, which will take place from June 8 to 22.
- CROI 2020Every year, CROI hosts some of the world's leading experts in HIV research, who come to present exciting new data and drive forward the field of HIV/AIDS research. This year, due to COVID-19, CROI held their meeting virtually.