Brief Report: Common Genetic Variation in Chromosome 10 q22.1 Shows a Strong Sex Bias in Human Embryonic Stem Cell Lines and Directly Controls the Novel Alternative Splicing of Human NODAL which is Associated with XIST Expression in Female Cell Lines
Bibliographic record
Abstract
The potential use of pluripotent stem cells for personalized regenerative medicine necessitates an improved understanding of how germ-line genetic variation may affect pluripotency. Given previous reports of a female bias in established human embryonic stem cell (hESC) lines, sex-specific differences must also be considered. Herein we describe, for the first time, how genetic polymorphisms may affect the establishment of widely used hESC lines. We demonstrate that the minor allele of the human single nucleotide polymorphism (SNP) rs2231947 found within the NODAL gene locus is under-represented in male but not female hESC lines. We also show that this SNP is highly functional in hESC lines. The SNP rs2231947 directly controls the alternative splicing of a novel NODAL transcript isoform. Thus we demonstrate that genetic variation drastically affects the expression of a gene that plays a major role in the regulation of pluripotency and cell fate. Our work helps detail how genetic heterogeneity is manifested in hESC biology and highlights the need to identify how specific genetic variants can explain important differences between pluripotent cell line models both within and between species.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".