Implications of genetic and epigenetic aberrations to the tumorigenicity of human pluripotent stem cells
Bibliographic record
Abstract
Human pluripotent stem cells (hPSCs) hold immense promise for cell replacement therapies due to their capacity to give rise to derivatives of the three embryonic germ layers and their ability to divide indefinitely in culture. Since their first derivation less than 30 years ago, multiple hPSC-derived cell products are already in clinical trials for a range of pathologies. Nevertheless, hPSCs also possess an intrinsic tumorigenic potential and have been shown to acquire recurrent genetic and epigenetic aberrations strongly associated with cancer initiation and progression. These properties cast doubt on the safety of hPSCs and raise concerns regarding their use for transplantation. In this review, we summarize the different kinds of genetic and epigenetic abnormalities repeatedly observed in hPSCs, how they emerge, and their potential implications for the tumorigenicity of hPSC-based products. We also discuss shared and unique abnormalities found in hPSCs derived from different sources. Finally, we suggest possible methods for reducing the occurrence of these aberrations and managing their effects once they arise.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".