Evidence map›Paper›PMID 39824186›Full record

ArticleStem cell reports2025

Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation.

Rony Chidiac, Andy Yang, Elli Kubarakos, Nicholas Mikolajewicz, Hong Han, Maira P Almeida, Pierre E Thibeault, Sichun Lin, Graham MacLeod, Jean-Philippe Gratton and 2 more

Abstract read
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In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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

12 authors.

Rony ChidiacDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Andy YangDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Elli KubarakosDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Nicholas MikolajewiczProgram in Genetics and Genome Biology, The Hospital for Sick Kids, Toronto, ON, Canada.
Hong HanProgram in Genetics and Genome Biology, The Hospital for Sick Kids, Toronto, ON, Canada.
Maira P AlmeidaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Pierre E ThibeaultDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Sichun LinDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Graham MacLeodDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
Jean-Philippe GrattonDepartment of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Jason MoffatProgram in Genetics and Genome Biology, The Hospital for Sick Kids, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Stephane AngersDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address: stephane.angers@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs). We found that FZD2 and FZD7 receptors are expressed at the membrane of hPSCs and that their activation triggers β-catenin signaling with different kinetics, thereby influencing mesoderm patterning choices. Specifically, FZD7 activation enhances both paraxial and lateral mesoderm differentiation, whereas FZD2 activation favors paraxial mesoderm. Mechanistically, FZD2 activation promotes sustained Wnt-β-catenin levels, guiding hPSCs differentiation toward paraxial mesoderm, while blocking lateral mesoderm. In contrast, FZD7 activation kinetics display similar initial activation but more dampening of β-catenin signaling, permitting lateral mesoderm induction in addition to paraxial mesoderm specification. Our findings reveal non-redundant roles for FZD2 and FZD7 in mesoderm specification, offering leverage for precise directed differentiation outcomes.

Indexed as

Cell DifferentiationFrizzled ReceptorsMesodermbeta CateninCell LineHumansPluripotent Stem CellsWnt Signaling Pathwaybeta CateninFrizzled ReceptorsFZD2 protein, humanFZD7 protein, humandirected differentiationFrizzled receptorshuman pluripotent stem cellsmesoderm specificationWnt agonistsWnt signaling

Identifiers

PMID39824186
PMCPMC11864152

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.