GeneSet Information

Tier IV GS409701 • Differentially expressed genes between GABA and Glutamatergic neurons in prefrontal cortex of control subjects (DE Glu)_pvalue

DESCRIPTION:

We employed our recently developed FANS-based protocol to isolate two types of neuronal nuclei: (1) the MGE-derived GABA neurons, and (2) glutamatergic neurons with a small (~10%) admixture of non-MGE derived GABA neurons (denoted “Glu neurons”). PFC tissue samples from 3 control subjects were used for the experiments. EdgeR R package was used to perform differential expression (DE) analysis between GABA and Glu neurons, with DE criteria of FDR < 0.01, abs(FoldChange) > 2, and a cutoff of 0.1 counts per million (CPM). From supplementary table 2.

LABEL:

DEG Glu PFC control_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

1300

DATE ADDED:

2024-12-11

DATE UPDATED:

2024-12-11

SPECIES:

AUTHORS:

Alexey Kozlenkov, Andrew E Jaffe, Alisa Timashpolsky, Pasha Apontes, Sergei Rudchenko, Mihaela Barbu, William Byne, Yasmin L Hurd, Steve Horvath, Stella Dracheva

TITLE:

DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age.

JOURNAL:

Genes May 2017, Vol 8, pp.

ABSTRACT:

We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0.001). DMSs and corresponding genes (DMGs) in heroin users showed significant differences in the preferential context of hyper and hypo DM. HyperDMSs were enriched in gene bodies and exons but depleted in promoters, whereas hypoDMSs were enriched in promoters and enhancers. In addition, hyperDMGs showed preference for genes expressed specifically by glutamatergic as opposed to GABAergic neurons and enrichment for axonogenesis- and synaptic-related gene ontology categories, whereas hypoDMGs were enriched for transcription factor activity- and gene expression regulation-related terms. Finally, we found that the DNAm-based "epigenetic age" of neurons from heroin users was younger than that in controls. Suicide-related results were more difficult to interpret. Collectively, these findings suggest that the observed DNAm differences could represent functionally significant marks of heroin-associated plasticity in the OFC. PUBMED: 28556790
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Annotation Information

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Social Control, Formal (D012926)
Gene Expression Regulation (D005786)
Exons (D005091)
Divorce (D004243)
DNA (D004247)
Street Drugs (D013287)
Tables (D020501)
gamma-Aminobutyric Acid (D005680)
Gene Expression (D015870)
Suicide (D013405)
Neurons (D009474)
Prefrontal Cortex (D017397)
Pharmaceutical Preparations (D004364)
Tissues (D014024)
Epigenomics (D057890)
Genes (D005796)
Transcription Factors (D014157)
Heroin (D003932)
Fluorescence (D005453)
DNA Methylation (D019175)
Methylation (D008745)
biological regulation (GO:0065007)
transcription, DNA-dependent (GO:0006351)
DNA methylation (GO:0006306)
methylation (GO:0032259)
transcription factor activity (GO:0003700)
gene expression (GO:0010467)
axonogenesis (GO:0007409)
Data acquisition and deposition (EDAM_topic:3077)
DNA methylation (EDAM_topic:3171)
Analysis (EDAM_operation:2945)
Ontology (EDAM_topic:0089)
Genetics (EDAM_topic:3053)
Experiment annotation (EDAM_data:2531)
dna (EDAM_format:1212)
Microarrays (EDAM_topic:0200)
Transcriptomics (EDAM_topic:0203)
Ontology (EDAM_data:0582)
Promoters (EDAM_topic:0111)
Transcription (EDAM_topic:0110)
Evidence (EDAM_data:2042)
Transcription factors and regulatory sites (EDAM_topic:0749)
DNA (EDAM_topic:0654)
deoxyribonucleic acid (CHEBI:16991)
gamma-aminobutyric acid (CHEBI:16865)
dilC18(5) dye (CHEBI:52027)
heroin (CHEBI:27808)
L-glutamic acid residue (CHEBI:29972)
advanced glycation end-product (CHEBI:84123)
drug (CHEBI:23888)
atomic nucleus (CHEBI:33252)
perfluorinated compound (CHEBI:134091)
glutamic acid (CHEBI:18237)
L-glutamic acid (CHEBI:16015)
evidence (ECO:0000000)
age (EFO:0000246)
suicide (EFO:0007624)
control (EFO:0001461)
orbitofrontal cortex (UBERON:0004167)
centro-posterior medial synaptic neuropil domain (UBERON:6007070)
cortex (UBERON:0001851)
medial ganglionic eminence (UBERON:0004024)
tissue (UBERON:0000479)
DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)
tissue (MA:0003002)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

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