Abstract 3354: Investigating the role of Nodal in the regulation of integrin α6β4high trophoblast progenitor cells
Notice bibliographique
Résumé
Abstract The human placenta is a highly invasive organ that invades the pregnant uterus to nourish the fetus. It develops from highly proliferative and phenotypically plastic cells called trophoblasts. Bi-potential trophoblast stem cells in the chorionic villi differentiate into the villous pathway to form the syncytiotrophoblast layer and the extravillous trophoblast (EVT). The HTR-8/SVneo cell line is widely used to study trophoblast biology. These cells simultaneously express villous-specific genes such as hCG and EVT-specific genes such as VE-Cadherin. Such phenotypic plasticity is indicative of a bi-potential cytotrophoblast progenitor. Preliminary work has shown that similar to the progenitors in situ, a subpopulation of HTR-8/SVneo cells expresses α6β4 integrin. This cell line also expresses Nodal, a stem cell-associated factor that sustains the pluripotency of embryonic stem cells and is re-expressed in certain cancers. We hypothesize that an α6β4high subset within HTR-8/SVneo cell line is enriched with bi-potential progenitors and that the stem cell-like properties of this population is maintained by Nodal signaling. Immunofluorescence microscopy and flow cytometry were used to confirm the presence of an α6β4high subpopulation in the HTR-8/SVneo cell line. Fluorescence Activated Cell Sorting (FACS) was used to purify α6β4high and α6β4low populations from the heterogeneous HTR-8/SVneo cells. The ability of α6β4high, α6β4low and heterogeneous (unsorted) HTR-8/SVneo populations to undergo self-renewal was determined using a limiting dilution clonogenic assay. Differentiation into endovascular-like trophoblast was assessed using a tube-formation assay on Matrigel and invasion assays, and differentiation into villous trophoblast was assessed by measuring α-hCG. The expression of Nodal in the α6β4 subtypes was assayed using Western blotting. We determined that approximately 25% of HTR-8/SVneo cells express α6β4 integrin protein on their cell surface. The α6β4high subpopulation had a significantly higher self-renewal capacity than the heterogeneous HTR-8/SVneo population and the α6β4low subpopulation had a lower clonogenic capacity relative to the α6β4high and heterogeneous cells. Nearly 100% of the α6β4high cells formed tubes when plated on Matrigel. In contrast, the unsorted HTR-8/SVneo cells formed tubes much less efficiently, and the α6β4low population was unable to undergo tube formation. The α6β4high population was also more invasive than the α6β4low cells, and Nodal was expressed to a greater level in the α6β4high population. Conclusions: Our results suggest that α6β4high sub-population in the HTR-8SV/neo cell line may represent a villous cytotrophoblast stem cell and that this subpopulation is enriched with Nodal. By understanding the mechanisms by which this subpopulation is regulated, we may glean insight into the regulation of invasive cancer stem cell populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3354. doi:1538-7445.AM2012-3354
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,003 | 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 ».