Low oxygen promotes extravillous trophoblast progenitor expansion but restrains maturation
Bibliographic record
Abstract
SUMMARY Placental development occurs in a low oxygen environment, yet how oxygen tension instructs differentiation of progenitor cytotrophoblasts (CTB) along the extravillous versus villous pathways remains incompletely understood. In particular, the role of low oxygen in early extravillous trophoblast (EVT) progenitor expansion and subsequent maturation has been difficult to assess due to the lack of models allowing sequential, high-resolution characterization. Using human trophoblast organoids and single-cell transcriptomics, we examined the effects of ambient (21%) and physiological (2–3%, 8%) oxygen on EVT and SCT differentiation. We show that low oxygen promotes the initial expansion of column CTB-like progenitors but restricts terminal EVT maturation. Conversely, we show that ambient oxygen drives the formation of EVT and syncytiotrophoblast. Stabilization of HIF-1 partially recapitulates the EVT maturation block but does not contribute to EVT progenitor expansion, indicating HIF-dependent and-independent contributions. These findings clarify how oxygen shapes EVT lineage progression and define HIF-1’s role in coordinating progenitor expansion versus maturation.
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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".