Immune-related transcriptomic and epigenetic reconfiguration in BV2 cells after LPS exposure: an in vitro omics integrative study
Bibliographic record
Abstract
Abstract Background Molecular alterations affecting microglia activity have been consistently associated with the inflammatory response. These cells can have pro or anti-inflammatory activity, phenotypes thought to be heavily regulated by epigenetic mechanisms. Still, little is known about the details on how epigenetic marks regulate the expression of genes in the context of an inflammatory response. Methods Through CUT&RUN, we profiled four genome-wide histone marks (HM) (H3K4me1, H3K4me3, H3K27ac and H3K27me3) in lipopolysaccharide exposed-cells and compared their distributions to control cells. Transcriptomic profiles were determined through RNA-seq and differentially expressed genes were identified and contrasted with the epigenetic landscapes. Other downstream analyses were also included in this study. Results Our results illustrate an effectively induced M1 phenotype in microglial cells derived from LPS exposure. We observed differential bound regions associated with genes classically involved in the inflammatory response in the expected direction according to each histone modification. Consistently, our transcriptomic analysis yielded a conspicuous illustration of the LPS-induced immune activity showing the up-regulation of Nf-κB induced mRNAs (TNF-α, nfκbiz, nfκbia) and other important genes (Marco, Il-6, etc.). Furthermore, we integrated both omics profiles and identified an important reconfiguration of the genome induced by LPS. The latter was depicted by 8 different chromatin states that changed between conditions and that, associated with unique clusters of differentially expressed genes, not only represented regulatory elements, but also underlined distinct biological functions (inhibition of morphogenesis; changes in metabolism, homeostasis, and cytokine regulation; activation of the inflammatory response). Conclusion This study exhibits important differences in the distribution of histone modifications in treated and control BV2 cells, constituting an epigenetic reconfiguration that leads to the inflammatory response. Also, it highlights the importance of these marks' regulatory role in gene expression and provides possible targets for further studies in the context of inflammation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".