Spatial heterogeneity of lactylation: insights into gene expression, metabolism, and lactate transport in human embryonic stem cells
Bibliographic record
Abstract
Low reprogramming efficiency and high phenotypic variability hinder the regenerative medicine applications of human pluripotent stem cells. Understanding the mechanisms that regulate pluripotency is crucial to overcoming these challenges. This study investigated the relationship between lactylation, a newly identified regulator of gene expression, pluripotency, metabolism, and lactate transport in human embryonic stem cells (hESCs). Histone lactylation levels were significantly higher in hESCs than in differentiated cells. Further, exogenous lactate increased histone lactylation and acetylation levels and altered pluripotency gene expression, notably increasing KLF4, KLF5, GBX2, and DMNT3L in hESCs. Finally, naïve-like hESC colonies exhibited higher lactylation levels peripherally, coinciding with elevated peripheral SOX2 levels. Conversely, lactate transport and production protein levels were higher centrally. This study suggests that elevated histone lysine lactylation levels are a newly identified characteristic of human pluripotency. The spatial distribution findings are consistent with a positive relationship between histone lactylation and SOX2 expression in naïve-like hESCs.
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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".