GEO series
Multi-tier signaling and epigenomic reprogramming drive microglial inflammatory states and functions associated with demyelination [ATAC-seq]
GSE302858
Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
42 samples
Submitted 2026/04/29
Platform GPL34290
Summary
The extensive heterogeneity of microglia inflammatory states accompanying neurodegenerative diseases underscores the complex molecular mechanisms that regulate these cells. Here, we report on transcriptional effectors that control microglial inflammatory state polarization associated with brain demyelination in mice. Using flow cytometry, microscopy and RNA-seq, we identified two dominant, functionally distinct states of Clec7a+CD229+ inflammatory microglia, discriminated from one another by CD11c expression. Epigenomic analyses implicated extensive genome-wide nucleosome remodeling to the polarization process, driven by state-associated stimulation of transcription factors that included Pu.1, AP-1, Bhlhe40 and Egr2, as well as re-calibration of homeostatic input provided by Mef2. Notably, a H3K27me3-based epigenetic gatekeeping mechanisms controls transcription of Egr2 and Bhlhe40 genes. Loss-of-function experiments validated the physiological relevance of Trem2, Mef2a and Egr2 to the microglial inflammatory state polarization process in the demyelinating brain. Therefore, distinct configuration of transcriptional input cooperate with epigenetic mechanisms to specify microglial inflammatory states and functions.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE302858_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 42 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1292474 and SRA study SRP601444. Searching any of these in the dataset finder brings you back here.
Study design
40 conditions, each sampled once — no replicated groups
Read from the first 40 of 42 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM9112429 ATACseq_Microglia_WT_Male_Adult_Basal_rep1_BC23_R1
- GSM9112430 ATACseq_Microglia_WT_Male_Adult_Basal_rep2_BC6_R1
- GSM9112431 ATACseq_Microglia_WT_Male_Adult_Basal_rep3_BC24_R1
- GSM9112432 ATACseq_Microglia_CD229NegativeCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep1_BC5_R1
- GSM9112433 ATACseq_Microglia_CD229NegativeCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep2_BC17_R1
- GSM9112434 ATACseq_Microglia_CD229NegativeCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep3_BC1_R1
- GSM9112435 ATACseq_Microglia_CD229PositiveCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep1_BC12_R1
- GSM9112436 ATACseq_Microglia_CD229PositiveCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep2_BC10_R1
- GSM9112437 ATACseq_Microglia_CD229PositiveCD11cNegative_WT_Male_Adult_Cuprizone_4w_rep3_BC2_R1
- GSM9112438 ATACseq_Microglia_CD229PositiveCD11cPositive_WT_Male_Adult_Cuprizone_4w_rep1_BC8_R1
- GSM9112439 ATACseq_Microglia_CD229PositiveCD11cPositive_WT_Male_Adult_Cuprizone_4w_rep2_BC11_R1
- GSM9112440 ATACseq_Microglia_CD229PositiveCD11cPositive_WT_Male_Adult_Cuprizone_4w_rep3_BC3_R1
- GSM9112441 ATACseq_Microglia_Trem2KO_Male_Adult_Basal_rep1_BC1_R1
- GSM9112442 ATACseq_Microglia_Trem2KO_Male_Adult_Basal_rep2_BC20_R1
- GSM9112443 ATACseq_Microglia_CD229NegativeCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep1_BC7_R1
- GSM9112444 ATACseq_Microglia_CD229NegativeCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep2_BC6_R1
- GSM9112445 ATACseq_Microglia_CD229NegativeCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep3_BC25_R2
- GSM9112446 ATACseq_Microglia_CD229PositiveCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep1_BC8_R1
- GSM9112447 ATACseq_Microglia_CD229PositiveCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep2_BC7_R1
- GSM9112448 ATACseq_Microglia_CD229PositiveCD11cNegative_Trem2KO_Male_Adult_Cuprizone_4w_rep3_BC22_R2
- GSM9112449 ATACseq_Microglia_Cx3cr1Cre_Male_Adult_Basal_rep1_BC5_R1
- GSM9112450 ATACseq_Microglia_Cx3cr1Cre_Male_Adult_Basal_rep2_BC12_R1
- GSM9112451 ATACseq_Microglia_Cx3cr1Cre_Male_Adult_Basal_rep3_BC13_R1
- GSM9112452 ATACseq_Microglia_Cx3cr1Cre_Male_Adult_Basal_rep4_BC1_R1
- GSM9112453 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cNegative_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep1_BC3_R1
- GSM9112454 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cNegative_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep2_BC2_PE150_R1
- GSM9112455 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cNegative_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep3_BC6_PE150_R1
- GSM9112456 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cPositive_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep1_BC8_R1
- GSM9112457 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cPositive_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep2_BC4_R1
- GSM9112458 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cPositive_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep3_BC3_PE150_R1
- GSM9112459 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cPositive_Cx3cr1Cre_Male_Adult_Cuprizone_5w_rep4_BC10_PE150_R1
- GSM9112460 ATACseq_Microglia_Cx3cr1Mef2aKO_Male_Adult_Basal_rep1_BC8_R1
- GSM9112461 ATACseq_Microglia_Cx3cr1Mef2aKO_Male_Adult_Basal_rep2_BC19_R1
- GSM9112462 ATACseq_Microglia_CD229Negative_Cx3cr1Mef2aKO_Male_Adult_Basal_rep1_BC8_PE150_R1
- GSM9112463 ATACseq_Microglia_CD229Negative_Cx3cr1Mef2aKO_Male_Adult_Basal_rep2_BC12_PE150_R1
- GSM9112464 ATACseq_Microglia_CD229Positive_Cx3cr1Mef2aKO_Male_Adult_Basal_rep1_BC9_PE150_R1
- GSM9112465 ATACseq_Microglia_CD229Positive_Cx3cr1Mef2aKO_Male_Adult_Basal_rep2_BC13_PE150_R1
- GSM9112466 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cNegative_Cx3cr1Mef2aKO_Male_Adult_Cuprizone_5w_rep1_BC15_R1
- GSM9112467 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cNegative_Cx3cr1Mef2aKO_Male_Adult_Cuprizone_5w_rep2_BC17_R1
- GSM9112468 ATACseq_Microglia_Clec7aPositiveCD229PositiveCD11cPositive_Cx3cr1Mef2aKO_Male_Adult_Cuprizone_5w_rep1_BC16_R1
+ 2 more — browse all 42 samples with per-sample file links →
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