TWIST Is a Key Molecular Regulator of Cadherin-Dependent Terminal Differentiation of Human Trophoblastic Cells In Vitro.
Bibliographic record
Abstract
The formation of the multinucleated syncytial trophoblast of the human placenta by the terminal differentiation and fusion of mononucleate villous cytotrophoblasts and the invasion of extravillous cytotrophoblasts (EVTs) into the underlying maternal tissues and vasculature are key steps in human placentation. The molecular mechanisms underlying the development of an invasive phenotype in EVTs include many of those first identified as having a role in cancer cell metastasis. Previous studies from our laboratory have demonstrated that a cellular event involved in syncytial trophoblast formation is the continuous and progressive decrease in expression of the cell-adhesion molecule E-CADHERIN (E-CAD). In view of these observations, and the integral role of the basic helix-loop-helix transcription factor TWIST in the onset and progression of cancer in a wide variety of tissues, we have examined the expression, regulation and function of TWIST in human trophoblastic cells in vitro. Our initial studies using Western blotting and immunofluorescent staining revealed that TWIST and E-CAD expression in cultured BeWo cells are differentially regulated by the second messenger cyclic AMP. Similarly, interleukin-1beta and transforming growth factor-beta1, two cytokines which promote and restrain human trophoblastic cell invasion respectively, were found to differentially regulate TWIST expression in primary cultures of EVTs in time-dependent manner. Gain- and loss-of-function studies were respectively performed using either a mammalian expression vector containing a cDNA encoding Twist or siRNA specific for this transcription factor. Our results show that Twist promotes the formation of the syncytial trophoblast through down-regulation of E-CAD, and promotes the invasive ability of EVTs through up-regulating N-CADHERIN (N-CAD) expression. Collectively, our findings demonstrate that TWIST is a key regulator of cadherin-mediated terminal differentiation of human trophoblastic cells. This research was funded by a grant from the Canadian Institutes of Health Research (CDM). YHN is the recipient of a studentship from the Child and Family Research Institute. (platform)
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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) | 0.002 | 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".