Evidence map›Paper›PMID 40335707›Full record

ArticleNature methods2025

Extended culture of 2D gastruloids to model human mesoderm development.

Bohan Chen, Hina Khan, Zhiyuan Yu, LiAng Yao, Emily Freeburne, Kyoung Jo, Craig Johnson, Idse Heemskerk

Abstract read
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In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
  5. Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Review
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Bohan ChenDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9781-2982
Hina Khan *Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Zhiyuan Yu *Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
LiAng Yao *Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Emily FreeburneDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Kyoung JoDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Craig JohnsonDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-3955-7394
Idse HeemskerkDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. iheemske@umich.edu.ORCID http://orcid.org/0000-0002-8861-7712

Funding

Multifunctional morphogens: patterning precision and mesoderm migrationR35GM138346 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HEEMSKERK, IDSE JOANNES · 2020 to 2025
$4.3M
National Science Foundation (NSF) 2033654U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM138346
6 · The paper itself

Abstract

Micropatterned human pluripotent stem cells treated with BMP4 (two-dimensional (2D) gastruloids) are among the most widely used stem cell models for human gastrulation. Due to its simplicity and reproducibility, this system is ideal for high-throughput quantitative studies of tissue patterning and has led to many insights into the mechanisms of mammalian gastrulation. However, 2D gastruloids have been studied only up to about 2 days owing to a loss of organization beyond this time with earlier protocols. Here we report an extended 2D gastruloid model to up to 10 days. We discovered a phase of highly reproducible morphogenesis between 2 and 4 days during which directed migration from the primitive streak-like region gives rise to a mesodermal layer beneath an epiblast-like layer. Multiple types of mesoderm arise with striking spatial organization including lateral plate mesoderm-like cells on the colony border and paraxial mesoderm-like cells further inside the colony. Single-cell transcriptomics showed strong similarity of these cells to mesoderm in human and nonhuman primate embryos. Our results illustrate that extended culture of 2D gastruloids provides a powerful model for human mesoderm differentiation and morphogenesis.

Indexed as

Cell Culture TechniquesGastrulationMesodermOrganoidsAnimalsBone Morphogenetic Protein 4Cell DifferentiationGastrulaHumansMorphogenesisPluripotent Stem CellsBMP4 protein, humanBone Morphogenetic Protein 4

Identifiers

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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.