Single-cell genomics identifies cell type–specific molecular changes in autism
By Dmitry Velmeshev, Lucas Schirmer, Diane Jung, Maximilian Haeussler, Y. Perez, Simone Mayer, A. Bhaduri, Nitasha Goyal, D. Rowitch, A. Kriegstein. Science, 2019
797 citations recorded by the source corpus.
Brain cell transcriptomes in autism Autism manifests in many ways. Despite that diversity, the disorder seems to affect specific cellular pathways, including those observed in the neocortex of patients' brains. Velmeshev et al. analyzed the transcriptomes of single brain cells, including neurons and glia, from patients with autism. Single-nucleus RNA sequencing analysis suggested that affected pathways regulate synapse function as well as neural outgrowth and migration. Furthermore, in patient samples, specific sets of genes enriched in upper-layer projection neurons and microglia correlated with clinical severity. Science, this issue p. 685 Single-cell analysis categorizes brain cell types most affected by autism and correlates transcriptional alterations with clinical symptoms. Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by autism has not been feasible until recently. We used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types. We found that synaptic signaling of upper-layer excitatory neurons and the molecular state of microglia are preferentially affected in autism. Moreover, our results show that dysregulation of specific groups of genes in cortico-cortical projection neurons correlates with clinical severity of autism. These findings suggest that molecular changes in upper-layer cortical circuits are linked to behavioral manifestations of autism.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1b1c68294414f9fe0f211fc5be403838cfe333b6
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In Molecular Biology
Citations in the corpus
- Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex (2020, methodology): “These layer-enriched expression associations for risk genes were largely independent of the enrichments seen comparing genes more highly expressed (WM: p=1.9e-29 and L1: p=4.5e-61) or more lowly expressed (L3: p=2.9e-5, L4: p=1.7e-42, L5: p=3.2e-36, and L6: p=1.9e-7) in brains of ASD patients compar”