Evidence map›Paper›PMID 39688759›Full record

ArticleStem cell reviews and reports2025

Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.

Georgia P Wong, Sunhild Hartmann, Olivia Nonn, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Natasha de Alwis, Ciara N Murphy, Natasha Pritchard, Ralf Dechend and 4 more

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Article in Stem cell reviews and reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Georgia P WongThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia. gpwong@student.unimelb.edu.au.ORCID 0000-0003-4131-0008
Sunhild HartmannThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Olivia NonnCharité- Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität, Berlin, Germany.
Ping CannonThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Tuong-Vi NguyenThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Manju KandelThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Natasha de AlwisThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Ciara N MurphyThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Natasha PritchardThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Ralf DechendCharité- Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität, Berlin, Germany.
Natalie J HannanThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
Stephen TongThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
David G SimmonsSchool of Biomedical Sciences, University of Queensland, Brisbane, Australia.
Tu'uhevaha J Kaitu'u-LinoThe Department of Obstetrics, Gynaecology and Newborn Health/Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.

Funding

Australian Research Council FT10100193Australian Research Council FT230100125National Health and Medical Research Council 2017897
6 · The paper itself

Abstract

Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist. We characterised LGR5/LGR4, their ligands/targets in human placenta, with further assessments on dysregulation in preeclampsia/fetal growth restriction (FGR). LGR5 mRNA was unaltered in first trimester (n = 11), preterm (n = 9) and term (n = 11) placental lysate. LGR5 was enriched in human trophoblast stem cells (hTSCs) and downregulated with differentiation to extravillous trophoblasts (p < 0.0215) and syncytiotrophoblasts (p < 0.0350). In situ hybridisation localised LGR5 to unique, proliferative MKI67 + mononuclear trophoblasts underlying syncytium which concurred with proposed progenitor identities in single-cell transcriptomics. LGR5 expression was significantly reduced in placentas from early-onset preeclampsia (p < 0.0001, n = 81 versus n = 19 controls), late-onset preeclampsia (p = 0.0046, n = 20 versus n = 33 controls) and FGR (p = 0.0031, n = 34 versus n = 17 controls). LGR4 was elevated in first trimester versus preterm and term placentas (p = 0.0412), in placentas with early-onset preeclampsia (p = 0.0148) and in FGR (p = 0.0417). Transcriptomic analysis and in vitro hTSC differentiation to both trophoblast lineages suggested LGR4 increases with differentiation. Single-nucleus RNA sequencing of placental villous samples supported LGR5 and LGR4 localisation findings. Hypoxia/proinflammatory cytokine treatment modelling elements experienced by the placenta in placental insufficiency pathogenesis did not significantly alter LGR5/LGR4. Ligands R-spondins 1/3/4, and neutralising targets ring finger protein 43 (RNF43) and zinc and ring finger 3 (ZNRF3) were also reduced in placentas from preeclamptic pregnancies. This study is the first to describe LGR5/LGR4 and their signalling partner expression in human placenta. Their dysregulations in the preeclamptic placenta allude to disruptions to integral trophoblast stem cell function/differentiation that may occur during placental development related to WNT signalling.

Indexed as

Pre-EclampsiaReceptors, G-Protein-CoupledSignal TransductionStem CellsAdultBiomarkersCell DifferentiationFemaleFetal Growth RetardationHumansPlacentaPregnancyTrophoblastsBiomarkersLGR4 protein, humanLGR5 protein, humanReceptors, G-Protein-CoupledLGR4LGR5PlacentaPreeclampsiaTrophoblast stem cellsWNT signalling

Identifiers

PMID39688759

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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.