OVO-Like 1 Is a Regulator of Human Trophoblast Differentiation.
Bibliographic record
Abstract
Trophoblast cells are phenotypically diverse epithelial cells that comprise the principal structural and functional components of the placenta. All trophoblast cells differentiate from common progenitor cells. However, studying human trophoblast differentiation has been hampered by an inability to stably culture human progenitor trophoblast cells. BeWo trophoblast cells are a human choriocarcinoma cell line that exhibit the capacity to differentiate into more mature trophoblast lineages following increases in intracellular 3'-5'-cyclic adenosine monophosphate (cAMP). Following exposure to 8-Bromo (8-Br)-cAMP, a cell permeable, non-hydrolyzable cAMP analog, BeWo cells exhibit some capacity to fuse together into a syncytium, whereas other cells aggressively invade Matrigel. Cells also exhibit endocrinological consistencies with differentiated trophoblast cells including the production of chorionic gonadotropin (CG). Therefore, cAMP-induced BeWo trophoblast cell differentiation has been used as a model to give insights into placental development in humans. We performed a microarray analysis comparing BeWo trophoblast cells cultured in the presence or absence of 8-Br-cAMP. Analysis was performed in triplicate; in total 232 genes increased >2-fold following a 24-h 8-Br-cAMP exposure, whereas 163 genes decreased >2-fold. In particular, microarray analysis revealed a dramatic induction of OVO-like 1 (OVOL1), a highly conserved zinc finger transcription factor that has been shown to play a crucial role in epithelial development and differentiation, most notably in keratinocytes. The role of this transcription factor in trophoblast development is not clear. Concomitant with induction of OVOL1 transcript expression, classical markers of trophoblast differentiation were also increased following BeWo exposure to 8-Br-cAMP, including CGA and CGB, matrix metalloproteinase 12 (MMP12), the transcription factor HOPX, and ERVFRD1 (Syncytin 2). These results were verified by qRT-PCR on independent samples. To investigate the role of OVOL1 in the regulation of 8-Br-cAMP-induced differentiation, trophoblast cells were stably transduced with lentivirus carrying PLKO.1 vectors encoding OVOL1-specific shRNAs. Control cells were infected with lentivirus carrying empty PLKO.1 vectors. Following 8-Br-cAMP exposure, OVOL1 shRNA-expressing trophoblast cells exhibited substantial knockdown of OVOL1 transcript, as well as functionally deficient responses of differentiated trophoblast cells including reduced invasion through Matrigel and impaired syncytialization. Moreover, transcript levels of CGA, CGB, MMP12, HOPX, and ERVFRD1 that were induced following 8-Br-cAMP exposure in control trophoblast cells were nullified in trophoblast cells expressing OVOL1-specific shRNA. In conclusion, OVOL1 plays a key role in 8-Br-cAMP-induced BeWo trophoblast differentiation and may be a key player in human placental development. This work was funded by NIH HD20676 (MJS). SJR is supported by a Canadian Institutes of Health Research Post-Doctoral Fellowship.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".