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Record W4392201311 · doi:10.1101/2024.02.22.581647

Placental cytotrophoblast microvillar stabilization is required for cell-cell fusion

2024· preprint· en· W4392201311 on OpenAlexaff
Wendy Duan, Sumaiyah Shaha, Khushali Patel, Ivan K. Domingo, Meghan Riddell

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicPregnancy and preeclampsia studies
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsCytotrophoblastSyncytiotrophoblastCell biologyCell fusionEzrinSyncytiumFusion mechanismBiologyLipid bilayer fusionCellChemistryPlacentaCytoskeletonBiochemistryFetusGeneticsMembrane

Abstract

fetched live from OpenAlex

Abstract The placenta is an essential organ of pregnancy required for maternal-fetal transport and communication. The surface of the placenta facing the maternal blood is formed by a single giant multinucleate cell: the syncytiotrophoblast. The syncytiotrophoblast is formed and maintained via fusion of progenitor cytotrophoblasts. Cell-cell fusion is a tightly regulated process, and in non-trophoblastic cells is accompanied by stereotypical alterations in cell shape by cells that have attained fusion-competence. The most prominent feature is the formation of actin-based membrane protrusions, but whether stereotypic morphological changes occur in fusion-competent cytotrophoblasts has not been characterized. Using a human placental explant model, we characterized cell shape factors associated with the attainment of cytotrophoblast fusion competence. We found that fusion-competent cytotrophoblasts are hypertrophic, elongated cells, that form microvilli at the apical membrane. The actin-membrane cross linker protein ezrin was found to have highly polarized expression within cytotrophoblast microvilli. Inhibition of ezrin activation destabilized cytotrophoblast microvilli and prevented cytotrophoblast fusion. Thus, we propose that the polarized activation of ezrin within apical microvilli and actin-mediated changes in membrane dynamics are necessary for cytotrophoblast fusion. Summary statement Fusion-competent cytotrophoblasts undergo dynamic changes in cell morphology including the acquisition of apically localized microvilli. Microvillar stabilization facilitates effective fusion and differentiation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.015
GPT teacher head0.232
Teacher spread0.217 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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