Single-cell genomics identifies cell type-specific molecular changes in autism.
Adolescent
Autistic Disorder
/ genetics
Cell Nucleus
/ metabolism
Child
Child, Preschool
Female
Gene Expression Profiling
Gene Expression Regulation
Genomics
/ methods
Humans
Male
Microglia
/ metabolism
Neocortex
/ metabolism
Neurons
/ metabolism
Sequence Analysis, RNA
Single-Cell Analysis
/ methods
Young Adult
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
17 05 2019
17 05 2019
Historique:
received:
22
10
2018
accepted:
12
04
2019
entrez:
18
5
2019
pubmed:
18
5
2019
medline:
18
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31097668
pii: 364/6441/685
doi: 10.1126/science.aav8130
pmc: PMC7678724
mid: NIHMS1053005
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
685-689Subventions
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH114825
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097305
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS103266
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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