NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE234520 Query DataSets for GSE234520
Status Public on Nov 05, 2023
Title Quantifying the neuronal and glial composition of the brain using DNA methylation profiles
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary To date, most epigenetic datasets have been generated on DNA samples isolated from bulk tissues. As the proportion of individual cell types within a sample can vary across individuals, systematic differences in cellular proportions that correlate with the phenotype of interest may manifest as differences in the overall epigenetic profile. Deconvolution algorithms calculate a series of continuous variables reflecting the underlying cellular heterogeneity of each sample from the bulk tissue profile that can be used to adjust for confounding in epigenome-wide association analyses. Here we provide novel reference profiles for brain cell types for use with reference based deconvolution algorithms. We used a FANS protocol recently described by our group to purify nuclei populations from prefrontal cortex tissue from 43 adult donors. Our initial gating strategy used an antibody against NeuN to isolate neuronal nuclei in combination with an antibody against SOX10 to separate oligodendrocyte nuclei from other glial nuclei. Subsequently, in a second gating strategy we additionally included an antibody against IRF8 to enrich microglia from the NeuNNeg/SOX10Neg fraction. Our third gating strategy used an antibody against SATB2 in place of NeuN to isolate excitatory neurons. We generated DNA methylation profiles using the Illumina EPIC array for NeuNPos (neuron-enriched; n = 28), NeuNNeg/SOX10Pos (oligodendrocyte-enriched; n = 24), NeuNNeg/SOX10Neg (microglia- and astrocyte-enriched; n = 21), NeuNNeg/SOX10Neg/IRF8Pos (microglia-enriched; n = 17), NeuNNeg/SOX10Neg/IRF8Neg, (astrocyte-enriched; n = 7), SATB2Pos (excitatory neuron-enriched; n = 9), and SATB2Neg (inhibitory neuron- and glial- enriched; n = 6) nuclei populations. We have demonstrated that these are applicable for use with established deconvolution algorithms to quantify the cellular heterogeneity of the cortex and other regions of the human brain from bulk DNAm data. These variables will be critical covariates to include in future epigenetic studies of brain disorders to minimise the risk of false positive associations and improve our understanding of the changes in the brain that underpin the development of psychiatric disorders and neurodegenerative diseases.
 
Overall design Post-mortem prefrontal cortex (PFC) samples were processed using our optimized FANS protocol to purify nuclei populations from 42 adult donors. Our initial gating strategy used an antibody against NeuN (a robust marker of post-mitotic neurons) to isolate neuronal nuclei in combination with an antibody against SOX10 (a transcription factor involved in the differentiation of oligodendrocytes) to separate oligodendrocyte nuclei from other glial nuclei. Subsequently, in a second gating strategy we additionally included an antibody against IRF8 (a transcription factor that is upregulated in microglia(30)) to enrich microglia from the NeuNNeg/SOX10Neg fraction. Our third gating strategy used an antibody against SATB2 (a DNA binding protein involved in transcriptional regulation and chromatin remodeling which is expressed in excitatory neurons in the mature central nervous system) in place of NeuN . We generated DNAm profiles using the Illumina EPIC array for NeuNPos (neuron-enriched; n = 28), NeuNNeg/SOX10Pos (oligodendrocyte-enriched; n = 24), NeuNNeg/SOX10Neg (microglia- and astrocyte-enriched; n = 21), NeuNNeg/SOX10Neg/IRF8Pos (microglia-enriched; n = 17), NeuNNeg/SOX10Neg/IRF8Neg, (astrocyte-enriched; n = 7), SATB2Pos (excitatory neuron-enriched; n = 9), and SATB2Neg (inhibitory neuron- and glial- enriched; n = 6) nuclei populations.
 
Contributor(s) Hannon E, Mill J
Citation(s) 38273288
Submission date Jun 08, 2023
Last update date Feb 04, 2024
Contact name Jonathan Mill
Organization name University of Exeter
Department Medical School
Street address RILD Building, RD&E Hospital
City Exeter
ZIP/Postal code EX2 5DW
Country United Kingdom
 
Platforms (1)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (112)
GSM7470185 EX16_Double-_S1
GSM7470186 EX17_Double-_S1
GSM7470187 EX18_Double-_S1
Relations
BioProject PRJNA981576

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234520_RAW.tar 1.5 Gb (http)(custom) TAR (of IDAT)
GSE234520_normMeth.csv.gz 1000.9 Mb (ftp)(http) CSV
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.