Evidence map›Paper›PMID 40844425›Full record

ArticleJournal of cell science2025

WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm.

Connor Ross, Paula A Balestrini, Lawrence E Bates, Takuya Azami, Taiye Adakole, Maxine Semple, Marika Salonna, Richard Gyuris, Jennifer Nichols, Norah E Fogarty and 1 more

Abstract read
In one paragraph

Article in Journal of cell science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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

11 authors.

Connor RossInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Paula A BalestriniCentre for Gene Therapy and Regenerative Medicine , King's College London, Tower Wing, Guy's Maze Pond, London SE1 9RT, UK.
Lawrence E BatesMRC Human Genetics Unit, Institute of Genetics and Cancer , The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Takuya AzamiMRC Human Genetics Unit, Institute of Genetics and Cancer , The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.ORCID 0000-0002-3759-9710
Taiye AdakoleGuy's Assisted Conception Unit, Division of Women's Health, School of Medicine , King's College London, London SE1 9RT, UK.
Maxine SempleGuy's Assisted Conception Unit, Division of Women's Health, School of Medicine , King's College London, London SE1 9RT, UK.
Marika SalonnaInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Richard GyurisInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Jennifer NicholsMRC Human Genetics Unit, Institute of Genetics and Cancer , The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.ORCID 0000-0002-8650-1388
Norah E FogartyCentre for Gene Therapy and Regenerative Medicine , King's College London, Tower Wing, Guy's Maze Pond, London SE1 9RT, UK.
Stefan HopplerInstitute of Medical Sciences, Foresterhill Health Campus, University of Aberdeen, Aberdeen AB25 2ZD, UK.ORCID 0000-0003-0730-4798

Funding

Biotechnology and Biological Sciences Research Council BB/Y001974/1Biotechnology and Biological Sciences Research Council BB/Y005120/1Medical Research Council 2117379UK Research and Innovation MR/W006693/1University of Aberdeen
6 · The paper itself

Abstract

Embryonic stem (ES) cell research has uncovered different requirements for WNT/β-catenin signalling in human naïve pluripotent cells compared to the mouse paradigm. It is therefore important to study WNT/β-catenin signalling directly in models that recapitulate early human development. Since TCF/LEF transcription factors mediate regulation of target genes downstream of WNT/β-catenin signalling, we examined the regulation, expression and protein localisation of the four TCF/LEF genes by analysing in vitro 'snapshots' of human development, leveraging naïve and primed pluripotent cells, blastoids and preimplantation blastocysts. Strikingly, we comprehensively confirm clear differences between mouse and human pluripotent stem cells, suggesting their differential requirements for WNT signalling reflects a pluripotent state-dependent manner. Human naïve ES cells express considerably lower levels of TCF7L1, unlike their mouse counterparts. TCF7L2 is robustly expressed in the trophectoderm derived from naïve ES cells, in blastoids and human preimplantation blastocysts. In primed pluripotent stem cells, active WNT/β-catenin signalling induces the expression of both TCF7 and LEF1, concomitant with hallmark gastrulation markers. The expression of human TCF/LEF genes indicates a differential requirement for WNT/β-catenin signalling throughout early human embryo development that warrants further investigation.

Indexed as

Cell LineageGene Expression Regulation, DevelopmentalLymphoid Enhancer-Binding Factor 1Pluripotent Stem CellsTranscription Factor 7-Like 1 ProteinTranscription Factor 7-Like 2 ProteinWnt Signaling PathwayAnimalsCell LineGerm LayersHumansMiceLymphoid Enhancer-Binding Factor 1TCF7L1 protein, humanTcf7l1 protein, mouseTCF7L2 protein, humanTranscription Factor 7-Like 1 ProteinTranscription Factor 7-Like 2 ProteinEarly embryonic cell lineagesExtra-embryonic cell lineagesHuman developmentNaïve pluripotencyTCF/LEF transcription factorsWNT/β-catenin signalling

Identifiers

PMID40844425
PMCPMC12516193

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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.