TPX2 Induces Mitotic Survival via BCL2L1 Induction Through YAP1 Protein Stabilization in Human Embryonic Stem Cells
Bibliographic record
Abstract
Abstract Genetic alterations have been reported in most human embryonic stem cells (hESCs) for decades. ‘Survival advantage,’ a typical trait acquired during long-term in vitro culture, results from induction of BCL2L1 upon frequent copy number variation (CNV) at locus 20q11.21 and is one of the strongest candidates associated with genetic alteration via escape from mitotic stress. However, the underlying mechanisms for BCL2L1 induction remain undefined. Furthermore, abnormal mitosis and ‘survival advantage’ frequently occurring in the late passage are respectively associated with the expression of TPX2 and BCL2L1, which are located in locus 20q11.21. In this study, we observed that 20q11.21 CNV was not sufficient for BCL2L1 induction and consequent survival traits in pairs of hESCs and human induced pluripotent stem cells (iPSCs) with normal and 20q11.21 CNVs. Inducible expression of TPX2 and basal TPX2 expression due to leakage of the inducible system in hESCs with normal copy number was sufficient to promote BCL2L1 expression and promoted high tolerance to mitotic stress. High Aurora A kinase activity by TPX2 stabilized YAP1 protein to promote YAP1 dependent BCL2L1 expression. Thus, a chemical inhibitor of Aurora A kinase and knockdown of YAP/TAZ significantly abrogated the aforementioned high tolerance to mitotic stress through BCL2L1 suppression. These results suggest that the collective expression of TPX2 and BCL2L1 from CNV at loci 20q11.21 and a consequent increase in YAP1 signaling would promote genome instability during long-term in vitro hESC culture.
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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) | 0.000 | 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) | 0.001 | 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".