Evidence map›Paper›PMID 31634368›Full record

ArticlePLoS biology2019

High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation-associated versus preneurulation-associated fate patterning.

Mukul Tewary, Dominika Dziedzicka, Joel Ostblom, Laura Prochazka, Nika Shakiba, Tiam Heydari, Daniel Aguilar-Hidalgo, Curtis Woodford, Elia Piccinini, David Becerra-Alonso and 7 more

Abstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

  1. Article
  2. From genes to germ layers: virtual twins of gastruloids.NPJ systems biology and applications · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction.Frontiers in cell and developmental biology · 2022
    Review
  18. Article
  19. Review
  20. Review
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

17 authors.

Mukul TewaryInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
Dominika DziedzickaResearch Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Joel OstblomInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-0051-3239
Laura ProchazkaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
Nika ShakibaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
Tiam HeydariMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.ORCID 0000-0003-0465-8312
Daniel Aguilar-HidalgoMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.ORCID 0000-0003-1366-9574
Curtis WoodfordInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
Elia PiccininiInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
David Becerra-AlonsoDepartment of Quantitative Methods, Universidad Loyola Andalucia, Sevilla, Spain.ORCID 0000-0001-5174-7743
Alice VickersCentre for Stem Cells & Regenerative Medicine, King's College London, London, United Kingdom.ORCID 0000-0001-9149-4744
Blaise LouisCentre for Stem Cells & Regenerative Medicine, King's College London, London, United Kingdom.ORCID 0000-0002-5289-2245
Nafees RahmanInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.
Davide DanoviCentre for Stem Cells & Regenerative Medicine, King's College London, London, United Kingdom.ORCID 0000-0003-4119-5337
Mieke GeensResearch Group Reproduction and Genetics, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.ORCID 0000-0003-2849-1406
Fiona M WattCentre for Stem Cells & Regenerative Medicine, King's College London, London, United Kingdom.ORCID 0000-0001-9151-5154
Peter W ZandstraInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-2356-942X

Funding

CIHR 375257Medical Research Council MC_PC_12026Medical Research Council MR/P018823/1Wellcome TrustWellcome Trust 206439/Z/17/Z
6 · The paper itself

Abstract

In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation-like fate patterning upon bone morphogenetic protein 4 (BMP4) treatment of geometrically confined colonies and observed significant heterogeneity in their differentiation propensities along a gastrulation associable and neuralization associable axis. This cell line-associated heterogeneity was found to be attributable to endogenous Nodal expression, with up-regulation of Nodal correlated with expression of a gastrulation-associated gene profile, and Nodal down-regulation correlated with a preneurulation-associated gene profile expression. We harness this knowledge to establish a platform of preneurulation-like fate patterning in geometrically confined hPSC colonies in which fates arise because of a BMPs signalling gradient conveying positional information. Our work identifies a Nodal signalling-dependent switch in peri-gastrulation versus preneurulation-associated fate patterning in hPSC cells, provides a technology to robustly assay hPSC differentiation outcomes, and suggests conserved mechanisms of organized fate specification in differentiating epiblast and ectodermal tissues.

Indexed as

Gene Expression Regulation, DevelopmentalBiomechanical PhenomenaBody PatterningBone Morphogenetic Protein 4Cell Culture TechniquesCell DifferentiationCell LineCell LineageGastrulationGene Expression ProfilingGenetic HeterogeneityHigh-Throughput Screening AssaysHumansModels, BiologicalNeurogenesisNodal ProteinBMP4 protein, humanBone Morphogenetic Protein 4Nodal ProteinNODAL protein, human

Identifiers

PMID31634368
PMCPMC6822778

What OpenQuestion holds

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LicenceCC BY
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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.