High‐mobility‐group protein 2 regulated by microRNA‐127 and small heterodimer partner modulates pluripotency of mouse embryonic stem cells and liver tumor initiating cells
Bibliographic record
Abstract
High‐mobility‐group protein 2 (HMGB2) expression is up‐regulated in human liver cancer; however, little is known about its regulatory function. Here, we establish HMGB2 as a new modulator of the pluripotency of mouse embryonic stem cells. Similar to octamer‐binding transcription factor 4 (OCT4) and sex‐determining region Y‐box 2 (SOX2), HMGB2 protein is highly expressed in undifferentiated CGR8 cells, whereas it undergoes rapid decline during embryonic body formation. HMGB2 interacts with OCT4, increases protein expression of OCT4 and SOX2, and enhances their transcriptional activities. We also show that microRNA (miRNA)‐127 is a translational repressor of HMGB2 protein expression by targeting its 3′ untranslated region. We further elucidate a transcriptional mechanism controlling HMGB2 messenger RNA expression by the nuclear receptor small heterodimer partner (SHP) and transcription factor E2F1. Diminishing HMGB2 expression by ectopic expression of miR‐127 or SHP or treatment with the small molecule inhibitor inflachromene decreases OCT4 and SOX2 expression and facilitates CGR8 differentiation. In addition, HMGB2 is markedly induced in liver tumor initiating cells. Diminishing HMGB2 expression by short hairpin RNA for HMGB2 (shHMGB2), miR‐127, or SHP impairs spheroid formation. Importantly, HMGB2 expression is elevated in various human cancers. Conclusion : HMGB2 acts upstream of OCT4/SOX2 signaling to control embryonic stem cell pluripotency. Diminishing HMGB2 expression by miR‐127 or SHP may provide a potential means to decrease the pluripotency of tumor initiating cells. ( Hepatology Communications 2017;1:816–830)
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".