5-azacytidine reactivates pluripotency gene expression, affects TET2 and histone transcription and modifies chromatin organization and morphology of mammal skin fibroblasts
Bibliographic record
Abstract
Phenotype expression is controlled by epigenetic regulations that guide cells through differentiation. The process is reversible and cells can be driven back to a higher plasticity state with the use of epigenetic modifiers. In this work we exposed skin fibroblasts to the demethylating agent 5-azacytidine (5-aza-CR), which is a well-known DNA methyltransferase inhibitor, and has been recently shown to increase cell plasticity and facilitate phenotype changes in different cell types (Pennarossa, 2013; Brevini, 2014; Pennarossa, 2014; Brevini, 2016). Although many aspects controlling its demethylating action have been widely investigated, the mechanisms through which 5-aza-CR acts on cell plasticity are still poorly understood. At the end of 5-aza-CR treatment, cells were divided in three experimental groups and cultured for 24 and 48 hours: A) cells were returned in standard fibroblast medium; B) cells were cultured in medium specific for pluripotency maintenance; C) cells were placed in a medium encouraging pancreatic differentiation. At the end of the culture period, as expected, we could observe a global demethylating effect. In parallel, however we detected a transient upregulation of the pluripotency genes OCT4, NANOG and REX1. Increased transcription of TET2 and histones belonging to the 1,2,3 and 4 families, together with changes in the expression of enzymes controlling histone acetylation were also appreciated. Interestingly, these results were accompanied by morphological and ultrastructural changes as well as by chromatin structure modifications. All together our findings indicate that 5-aza-CR induced somatic cell transition to a higher plasticity state involves novel cellular targets that activate multiple epigenetic regulatory pathways.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".