ArticleScientific reports2021
Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells.Nature biotechnology · 2026Article
- ESRG maintains human pluripotent stem cell self-renewal by binding NPM1 to regulate BMP4 protein and TGF-β signaling pathway.Cell & bioscience · 2026Article
- Induction of SOX17 with stimulation of WNT, TGF-beta, and FGF signaling drives embryonal carcinomas into the yolk-sac tumor lineage resulting in increased cisplatin resistance.International journal of cancer · 2025Article
- Extraembryonic mesoderm cells derived from human embryonic stem cells rely on Wnt pathway activation.Cell proliferation · 2025Article
- Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs.Cell and tissue research · 2023Article
- The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation.Stem cell reports · 2023Article
- Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells.Cell stem cell · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain endoderm derivatives, differentiating instead into extra-embryonic mesoderm. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signalling. Modulation of these pathways with small molecules confirmed them as the cause of the differentiation impairment. While activation of WNT and BMP4 in control cells resulted in a loss of endoderm differentiation and induction of extra-embryonic mesoderm markers, inhibition of these pathways in the subline restored its ability to differentiate. Karyotyping and exome sequencing analysis did not identify any changes in the genome that could account for the pathway deregulation. These findings add to the increasing evidence that different responses of stem cell lines to differentiation protocols are based on genetic and epigenetic factors, inherent to the line or acquired during cell culture.
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