Short Telomeres in ESCs Lead to Unstable Differentiation
Bibliographic record
Abstract
Functional telomeres are critical for stem cell proliferation; however, whether they are equally important for the stability of stem cell differentiation is not known. We found that mouse embryonic stem cells (ESCs) with critically short telomeres (Tert(-/-) ESCs) initiated normal differentiation after leukemia inhibitory factor (LIF) withdrawal but, unlike control ESCs, failed to maintain stable differentiation when LIF was reintroduced to the growth medium. Tert(-/-) ESCs expressed higher levels of Nanog and, overall, had decreased genomic CpG methylation levels, which included the promoters of Oct4 and Nanog. This unstable differentiation phenotype could be rescued by telomere elongation via reintroduction of Tert, via suppression of Nanog by small hairpin RNA (shRNA) knockdown, or via enforced expression of the de novo DNA methyltransferase 3b. These results demonstrate an unexpected role of functional telomeres in the genome-wide epigenetic regulation of cell differentiation and suggest a potentially important role of telomere instability in cell fate during development or disease.
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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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".