Evidence map›Paper›PMID 31263269›Full record

ArticleNature cell biology2019

A 3D model of a human epiblast reveals BMP4-driven symmetry breaking.

Mijo Simunovic, Jakob J Metzger, Fred Etoc, Anna Yoney, Albert Ruzo, Iain Martyn, Gist Croft, Dong Shin You, Ali H Brivanlou, Eric D Siggia

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
8.7field-weighted citation impact, top 1% of its field
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

103 citing papers in PubMed, 182 citations in OpenAlex.

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  5. Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026
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  15. Review
  16. Pluripotent cell states and fates in human embryo models.Development (Cambridge, England) · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Article

43 more citing papers are in PubMed but not listed here.

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

10 authors at 1 institution in 1 country.

Mijo SimunovicLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-9394-1552
Jakob J MetzgerLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
Fred EtocLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-5859-2382
Anna YoneyLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
Albert RuzoLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
Iain MartynLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
Gist CroftLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
Dong Shin You
Ali H BrivanlouLaboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA. brvnlou@rockefeller.edu.ORCID http://orcid.org/0000-0002-1761-280X
Eric D SiggiaCenter for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA. siggiae@rockefeller.edu.ORCID http://orcid.org/0000-0001-7482-1854
Rockefeller University · US

Funding

Dynamic readout of TGFb signaling and modeling of cell fate specification in humaR01GM101653 · NIGMS · ROCKEFELLER UNIVERSITY · PI BRIVANLOU, ALI H, SIGGIA, ERIC D. · 2012 to 2020
$2.6M
Dissecting embryonic axis formation using micropatterned hESC colony architectureR01HD080699 · NICHD · ROCKEFELLER UNIVERSITY · PI BRIVANLOU, ALI H, SIGGIA, ERIC D. · 2014 to 2018
$1.7M
NICHD NIH HHS R01 HD080699NIGMS NIH HHS R01 GM101653
6 · The paper itself

Abstract

Breaking the anterior-posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT signalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.

Indexed as

Tissue Culture TechniquesBone Morphogenetic Protein 4Cell PolarityEpithelial-Mesenchymal TransitionGastrulationGene Expression Regulation, DevelopmentalGerm LayersHumansPrimitive StreakSignal TransductionBMP4 protein, humanBone Morphogenetic Protein 4

Identifiers

PMID31263269
OpenAlexW2954548460

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.