GEO series

Multimodal characterization of the effects of stimulation on the human brain ex vivo and in vivo.

GSE288939 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 60 samples Submitted 2026/06/06 Platform GPL34284

Summary

The underlying mechanisms of therapeutics using brain stimulation in humans are not understood. In particular, it is unknown how brain stimulation impacts gene expression in acute and chronic temporal periods. Although therapeutic approaches like deep brain stimulation are becoming more widely used, it is impossible to study stimulation-induced genetic changes without tissue samples which at best could be collected post-mortem. To overcome these extremely limiting circumstances, we have implemented a multi-part experimental design involving single cell resolution RNA and ATAC sequencing of human cortex that has been stimulated in several paradigms. In the first, acute human cortex slices are stimulated with a high-density microelectrode array, which allows us to track how neural activity changes after stimulation together with genomic changes. In the second, tissue is collected from neurosurgery patients immediately after direct cortical stimulation in vivo. We have uncovered differentially expressed genes and differentially accessible chromatin regions in both paradigms. We have also determined the impact of stimulation on cell assembly plasticity and celltype-specific changes in firing patterns. Our integrated approach of applying stimulation paradigms in human brain tissue both in vivo and ex vivo has not been completed before. These results represent a key first step in our quest to understand exactly how brain stimulation supports neural function at the cellular level.

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Direct links to NCBI, no account and no request form: the whole study as GSE288939_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 60 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1220064 and SRA study SRP562051. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly with about 6 replicates each

snRNAseq, In vivo control, donor IVS ×9 snATACseq, In vivo control, donor IVS ×7 snRNAseq, MEA control, donor MEA ×6 snATACseq, MEA control, donor MEA ×6 snRNAseq, MEA stimulation, donor MEA ×6 snATACseq, MEA stimulation, donor MEA ×6

Supports a between-group comparison across 40 samples.

6 replicated groups read from the first 40 of 60 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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