Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons
Lai, C.-Y.; Arzavala, J.; Duarte, A. P.; Wang, S.; Li, J.; Liu, H.; Osteen, J.; Castanon, R. G.; Nery, J. R.; Powell, S. B.; Ecker, J. R.; Mukamel, E. A.; Behrens, M. M.
Show abstract
Elevated levels of maternal pro-inflammatory cytokines during gestation can disrupt offspring neural development, increasing the risk of neurodevelopmental disorders. We studied the effects of Poly(I:C)-induced maternal immune activation (PIC-MIA) during mid-gestation on developing cortical excitatory neurons DNA methylation and transcriptome. PIC-MIA disrupted the developmental regulation of synapse-related genes and of genes implicated in autism spectrum disorders. Genomic regions that gain or lose DNA methylation during normal development were altered following PIC-MIA, including neurodevelopmental transcription factor binding sites. The DNA methylation and transcriptional changes were consistent with a delay in excitatory neuron maturation. Whole-cell recordings showed that PIC-MIA preferentially altered the physiological development of layer 5 excitatory neurons. Taken together, present results suggest that alterations in the epigenome, through the disruption of circuit formation, may drive the long-term consequences of maternal infection during gestation.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- MYT1L deficiency impairs excitatory neuron trajectory during cortical development 96%
- CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment 96%
- Cell-Type Specific Profiling of Histone Post-Translational Modifications in the Adult Mouse Striatum 96%
Similar papers in this journal
- Compensation between FOXP transcription factors maintains proper striatal function 96%
- Epigenetically bistable regions across neuron-specific genes govern neuron eligibility to a coding ensemble in the hippocampus 96%
- Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling 95%
Similar papers in this journal
- Cortical Organoids Model Early Brain Development Disrupted by 16p11.2 Copy Number Variants in Autism 96%
- Analyses of the Autism-associated Neuroligin-3 R451C Mutation in Human Neurons Reveals a Gain-of-Function Synaptic Mechanism 96%
- Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine 95%
Similar papers in this journal
- Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids 96%
- Top2a promotes the development of social behavior via PRC2 and H3K27me3 96%
- GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders 96%
Similar papers in this journal
- Weak parent-of-origin expression bias: is this imprinting? 95%
- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2G2019S model of Parkinson's disease 95%
- Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.