ArticleScientific reports2021
Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm.
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 9 papers.
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Who cites it
9 citing papers in PubMed, 38 citations in OpenAlex.
- The LINC01612-DVL2-WNT axis promotes human endoderm differentiation.Stem cell reports · 2025Article
- WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm.Journal of cell science · 2025Article
- ETVs dictate hPSC differentiation by tuning biophysical properties.Nature communications · 2025Article
- Article
- Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.Cell communication and signaling : CCS · 2024Article
- PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation.Cell communication and signaling : CCS · 2024Article
- A desert lncRNA HIDEN regulates human endoderm differentiation via interacting with IMP1 and stabilizing FZD5 mRNA.Genome biology · 2023Article
- Heparinized Gelatin-Based Hydrogels for Differentiation of Induced Pluripotent Stem Cells.Biomacromolecules · 2022Article
- Quantitative developmental biology in vitro using micropatterning.Development (Cambridge, England) · 2021Review
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low differentiation propensity towards a targeted lineage can significantly hamper the utility of individual human pluripotent stem cell (hPSC) lines in biomedical applications. Here, we use monolayer and micropatterned cell cultures, as well as transcriptomic profiling, to investigate how variability in signalling pathway activity between human embryonic stem cell lines affects their differentiation efficiency towards definitive endoderm (DE). We show that endogenous suppression of WNT signalling in hPSCs at the onset of differentiation prevents the switch from self-renewal to DE specification. Gene expression profiling reveals that this inefficient switch is reflected in NANOG expression dynamics. Importantly, we demonstrate that higher WNT stimulation or inhibition of the PI3K/AKT signalling can overcome the DE commitment blockage. Our findings highlight that redirection of the activity of Activin/NODAL pathway by WNT signalling towards mediating DE fate specification is a vulnerable spot, as disruption of this process can result in poor hPSC specification towards DE.
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