Format

Send to

Choose Destination
Science. 2019 May 17;364(6441):685-689. doi: 10.1126/science.aav8130.

Single-cell genomics identifies cell type-specific molecular changes in autism.

Author information

1
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA. dmitry.velmeshev@ucsf.edu arnold.kriegstein@ucsf.edu.
2
Department of Neurology, University of California, San Francisco, CA 94158, USA.
3
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
4
Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
5
Department of Neurology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
6
Genomics Institute, University of California, Santa Cruz, CA, USA.
7
Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
8
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
9
Department of Paediatrics and Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0QQ, UK.
10
Department of Neurosurgery, University of California, San Francisco, CA 94143, USA.

Abstract

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.

PMID:
31097668
DOI:
10.1126/science.aav8130

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center