Evidence map›Paper›PMID 42711263›Full record

ArticleMolecular human reproduction2026

Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures.

Michael Zheng, Lin Zhao, Richard Xi, Jahdiel DeNobrega, Mary Tammo, Stephen J Renaud, Peeyush K Lala

Abstract read
In one paragraph

Article in Molecular human reproduction, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Michael ZhengDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.ORCID 0000-0003-0968-689X
Lin ZhaoDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Richard XiDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Jahdiel DeNobregaDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Mary TammoDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Stephen J RenaudDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.ORCID 0000-0001-7257-5354
Peeyush K LalaDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.ORCID 0000-0002-6405-9584

Funding

Children's Health Research InstituteCIHR CIHR; PJT180483Natural Sciences and Engineering Research Council of Canada 04543-2023 RGPIN
6 · The paper itself

Abstract

Proper trophoblast development is essential for placental function and is a key determinant of pregnancy outcomes. Three-dimensional spheroid and organoid cultures using cells from placental tissues or trophoblast stem cells have emerged as models that recapitulate cell-cell interactions and aspects of the physiological environment. Trophoblast organoids typically contain self-renewing cytotrophoblasts located toward the periphery in contact with basement membrane, whereas cells within the core fuse into hormone-producing syncytiotrophoblasts. Removing cells from matrix and/or culturing them in suspension can reverse this organization. In both cases, spontaneous syncytialization occurs, but the underlying mechanisms remain poorly understood. To identify signaling pathways associated with spontaneous trophoblast differentiation in three-dimensional conditions, human trophoblast stem cells were either maintained in the stem state as two-dimensional (2D) monolayers or aggregated in suspension without an exogenous matrix to form three-dimensional cultures. Expression and localization of trophoblast subpopulation markers were compared between two- and three-dimensional cultures. Three-dimensional cultures displayed increased spontaneous differentiation into the syncytiotrophoblast lineage along the periphery, accompanied by reduced proliferation of cytotrophoblasts. Consistent with this observation, BeWo choriocarcinoma cells exhibited increased chorionic gonadotropin levels in three-dimensional culture, whereas this response was not observed in HTR8/SVneo immortalized trophoblasts. Gene expression and pathway enrichment analyses identified Hippo signaling as altered in three-dimensional trophoblast stem cell cultures, with reduced expression of several genes associated with YAP1/TAZ-TEAD transcriptional activity. Inhibition of LATS1/2, which activates YAP1/TAZ-TEAD signaling, reduced spontaneous syncytiotrophoblast formation. These findings suggest that reduced YAP1/TAZ-TEAD activity may facilitate self-organized syncytialization in three-dimensional trophoblast cultures.

Indexed as

Protein Serine-Threonine KinasesTrophoblastsAdaptor Proteins, Signal TransducingCell Culture Techniques, Three DimensionalCell DifferentiationCell ProliferationExtravillous TrophoblastsFemaleHippo Signaling PathwayHumansPlacentaPregnancySignal TransductionStem CellsTranscription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingProtein Serine-Threonine KinasesTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins3D cultureHippo signalinghuman placentaorganoidsyncytiotrophoblasttrophoblast differentiationtrophoblast stem cellsYAP1/TAZ

Identifiers

PMID42711263
PMCPMC13641821

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.