GEO series

Epigenomic and Functional Convergence Between Glucocorticoid- and IL4-Driven Macrophage Programming

GSE250376 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 13 samples Submitted 2024/09/03 Platform GPL24247

Summary

Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 (IL4) promoting a tissue-repair homeostatic state (M2IL4). Glucocorticoids, widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2GC), but how or to what extent these populations functionally converge is unknown. We show that M2IL4 and M2GC transcriptomes share a striking overlap mirrored by a shift in chromatin landscape in both common and signal-specific gene subsets. This core homeostatic program is enacted by transcriptional effectors KLF4 and the GC receptor, whose genome-wide occupancy and actions are integrated in a stimulus-specific manner by the nuclear receptor cofactor GRIP1. Indeed, many of the M2IL4:M2GC-shared transcriptomic changes were GRIP1-dependent. Consistently, GRIP1 loss attenuated phagocytic activity of both populations in vitro and macrophage tissue-repair properties in the murine colitis model in vivo. These findings provide a mechanistic framework for homeostatic macrophage programming by distinct signals, to better inform anti-inflammatory drug design.

Published in

Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming

Deochand DK, Dacic M, Bale MJ et al. · Nature communications 2024 · PMID 39424780 · doi:10.1038/s41467-024-52942-x

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Direct links to NCBI, no account and no request form: the whole study as GSE250376_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 13 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 PRJNA1053779 and SRA study SRP478461. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39424780) ↗

Study design

5 conditions, mostly in triplicate

GRIP1_Control ×3 GRIP1_Dex ×3 GRIP1_IL4 ×3 KLF4_Dex ×2 KLF4_IL4 ×2

Supports a between-group comparison across 13 samples.

5 replicated groups read from 13 sample titles; they account for 13 of them. Check it against the sample list below before relying on it.

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