The FOS Transcription Factor Family Differentially Controls Trophoblast Migration and Invasion
Bibliographic record
Abstract
Extravillous trophoblast invasion is a fundamental component of human placentation. Invading trophoblast cells promote blood flow to the conceptus by actively remodeling the uterine vasculature. The extent of trophoblast invasion is tightly regulated; aberrant invasion is linked with several obstetrical complications. However, the transcriptional networks responsible for controlling the extent of trophoblast invasion are not well defined. Previous studies have identified high levels of FOS (FOS, FOSB, FOS-like (FOSL) 1, and FOSL2) proteins in extravillous trophoblast cells. These proteins form part of the activating protein-1 (AP-1) transcription factor complex and are implicated in regulating gene networks controlling cellular invasion in diverse biological systems. Therefore, we hypothesized that FOS family proteins play a role in regulating trophoblast invasion. We assessed expression of FOS family proteins in trophoblast cell lines and human placentae at different gestational ages. FOS, FOSB, and FOSL1 proteins were robustly increased in trophoblast cells subject to wound-based migration assays as well as Matrigel-based invasion assays. FOS knockdown resulted in cessation of proliferation and an induction of migration and invasion concomitant with robust expression of matrix metalloproteinase (MMP) 1, MMP3, and MMP10. Conversely, FOSL1 knockdown abrogated trophoblast migration and invasion and inhibited the production of MMP1, MMP3, and MMP10. In human placenta, FOS was expressed in proximal anchoring villi in conjunction with phospho-ERK. FOSL1 was temporally expressed only in the distal-most extravillous trophoblast cells, which represent a migratory cell population. Therefore, FOS and FOSL1 exert opposing effects on trophoblast invasion.
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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".