OVO-Like 1 Is a Regulator of Human Trophoblast Differentiation.
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».