Evidence map›Paper›PMID 40424181›Full record

ArticleeLife2025

Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing.

Madeline M Keenen, Liheng Yang, Huan Liang, Veronica J Farmer, Rizban E Worota, Rohit Singh, Amy S Gladfelter, Carolyn B Coyne

Abstract readComparative Study
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

24 citing papers in PubMed.

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  11. Article
  12. Decoding Human Placental Cellular and Molecular Responses to Obesity and Fetal Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  13. Article
  14. Trophoblast ferroptosis restricts SARS-CoV-2 spread in the placenta.bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Review
  17. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Madeline M KeenenDuke University School of Medicine, Department of Cell Biology, Durham, United States.ORCID https://orcid.org/0000-0002-9585-3705
Liheng YangDuke University School of Medicine, Department of Integrative Immunobiology, Durham, United States.ORCID https://orcid.org/0000-0001-6842-086X
Huan LiangDuke University School of Medicine, Department of Cell Biology, Durham, United States.ORCID https://orcid.org/0009-0000-4846-2499
Veronica J FarmerDuke University School of Medicine, Department of Cell Biology, Durham, United States.ORCID https://orcid.org/0000-0003-3857-5793
Rizban E WorotaDuke University School of Medicine, Department of Integrative Immunobiology, Durham, United States.ORCID https://orcid.org/0009-0007-3732-8463
Rohit SinghDuke University School of Medicine, Department of Cell Biology, Durham, United States.ORCID https://orcid.org/0000-0002-4084-7340
Amy S GladfelterDuke University School of Medicine, Department of Cell Biology, Durham, United States.ORCID https://orcid.org/0000-0002-2490-6945
Carolyn B CoyneDuke University School of Medicine, Department of Integrative Immunobiology, Durham, United States.ORCID https://orcid.org/0000-0002-1884-6309

Funding

Innate immune signaling in placental antiviral defensesR01AI145828 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COYNE, CAROLYN B, DIAMOND, MICHAEL S · 2019 to 2023
$3.5M
Dissecting the mechanistic role of multinucleation in breast and trophoblast cancers K00CA245719 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KEENEN, MADELINE · 2021 to 2024
$363k
Howard Hughes Medical Institute HHMI Faculty Scholar awardNational Institute of Allergy and Infectious Diseases AI145828National Science Foundation NSF 743900NCI NIH HHS K00 CA245719NIAID NIH HHS R01 AI145828
6 · The paper itself

Abstract

The syncytiotrophoblast (STB) is a multinucleated cell layer that forms the outer surface of human chorionic villi. Its unusual structure, with billions of nuclei in a single cell, makes it difficult to resolve using conventional single-cell methods. To better understand STB differentiation, we performed single-nucleus and single-cell RNA sequencing on placental tissue and trophoblast organoids (TOs). Single-nucleus RNA-seq was essential for capturing STB populations, revealing three nuclear subtypes: a juvenile subtype co-expressing CTB and STB markers, one enriched in oxygen sensing genes, and another in transport and GTPase signaling. Organoids grown in suspension culture (STBout) showed higher expression of STB markers, hormones, and a greater proportion of the transport-associated nuclear subtype while TOs grown with an inverted polarity (STBin) exhibited a higher proportion of the oxygen sensing nuclear subtype. Gene regulatory analysis identified conserved STB markers, including the chromatin remodeler RYBP. Although RYBP knockout did not impair fusion, it downregulated CSH1 and upregulated oxygen-sensing genes. Comparing STB expression in first trimester, term, and TOs revealed shared features but context-dependent variability. These findings establish TOs as a robust platform to model STB differentiation and nuclear heterogeneity, providing insight into the regulatory networks that shape placental development and function.

Indexed as

OrganoidsPlacentaRNA, Small NuclearTrophoblastsCell DifferentiationFemaleHumansPregnancySequence Analysis, RNASingle-Cell AnalysisRNA, Small Nucleardevelopmental biologyhumanOrganoidsnRNA-Sequencingsyncytiotrophoblasttrophoblast

Identifiers

PMID40424181
PMCPMC12113261

What OpenQuestion holds

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Registered trials

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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.