ArticleeLife2018
WNT signaling memory is required for ACTIVIN to function as a morphogen in human gastruloids.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 85 citations in OpenAlex.
- TGFβ-dependent upregulation of OCIAD2 is essential for epithelial-to-mesenchymal transition during mesendoderm differentiation.Stem cell reports · 2026Article
- Dynamic control of cell state transitions during tissue morphogenesis.The EMBO journal · 2026Review
- A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability.Nature cell biology · 2026Article
- Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells.Nature biotechnology · 2026Article
- Elucidating the roles of microRNA-103a-3p in trophoblast invasion and SOX4-mediated extravillous differentiation induced by activin A.Cell death & disease · 2026Article
- Dependence of cell fate potential and cadherin switching on the coordinate within the primitive streak during differentiation of human pluripotent stem cells.Development (Cambridge, England) · 2026Article
- Optogenetic WNT signaling drives germ layer self-organization in a human gastruloid model.bioRxiv : the preprint server for biology · 2026Article
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- A human epiblast model reveals dynamic TGFβ-mediated control of epithelial identity during mammalian epiblast development.Nature cell biology · 2026Article
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- Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.Development (Cambridge, England) · 2025Article
- The emergence of human primordial germ cell-like cells in stem cell-derived gastruloids.Science advances · 2025Article
- Advances in micropatterning technology for mechanotransduction research.Mechanobiology in medicine · 2024Review
- β-catenin mediates endodermal commitment of human ES cells via distinct transactivation functions.Cell & bioscience · 2024Article
- Combinatorial interpretation of BMP and WNT controls the decision between primitive streak and extraembryonic fates.Cell systems · 2024Article
- Distinct pathways drive anterior hypoblast specification in the implanting human embryo.Nature cell biology · 2024Article
- Time-integrated BMP signaling determines fate in a stem cell model for early human development.Nature communications · 2024Article
- Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.bioRxiv : the preprint server for biology · 2024Article
- Article
- Modeling development using hydrogels.Development (Cambridge, England) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Self-organization of discrete fates in human gastruloids is mediated by a hierarchy of signaling pathways. How these pathways are integrated in time, and whether cells maintain a memory of their signaling history remains obscure. Here, we dissect the temporal integration of two key pathways, WNT and ACTIVIN, which along with BMP control gastrulation. CRISPR/Cas9-engineered live reporters of SMAD1, 2 and 4 demonstrate that in contrast to the stable signaling by SMAD1, signaling and transcriptional response by SMAD2 is transient, and while necessary for pluripotency, it is insufficient for differentiation. Pre-exposure to WNT, however, endows cells with the competence to respond to graded levels of ACTIVIN, which induces differentiation without changing SMAD2 dynamics. This cellular memory of WNT signaling is necessary for ACTIVIN morphogen activity. A re-evaluation of the evidence gathered over decades in model systems, re-enforces our conclusions and points to an evolutionarily conserved mechanism.
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Registered trials
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.