Evidence map›Paper›PMID 30829572›Full record

ArticleeLife2019

Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells.

Idse Heemskerk, Kari Burt, Matthew Miller, Sapna Chhabra, M Cecilia Guerra, Lizhong Liu, Aryeh Warmflash

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 123 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025
    Article
  9. Review
  10. Prespecified dental mesenchymal cells for the making of a tooth.International journal of oral science · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Optogenetic control of Nodal signaling patterns.Development (Cambridge, England) · 2025
    Article
  19. Review
  20. Article

8 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

7 authors at 1 institution in 1 country.

Idse HeemskerkDepartment of Biosciences, Rice University, Houston, United States.ORCID 0000-0002-8861-7712
Kari BurtDepartment of Biosciences, Rice University, Houston, United States.
Matthew MillerDepartment of Biosciences, Rice University, Houston, United States.
Sapna ChhabraSystems, Synthetic and Physical Biology Program, Rice University, Houston, United States.ORCID 0000-0002-2479-0911
M Cecilia GuerraDepartment of Biosciences, Rice University, Houston, United States.
Lizhong LiuDepartment of Biosciences, Rice University, Houston, United States.
Aryeh WarmflashDepartment of Biosciences, Rice University, Houston, United States.ORCID 0000-0002-5679-2268
Rice University · US

Funding

Cancer Prevention and Research Institute of Texas RR140073Gillson Longenbaugh Foundation 15-0217National Science Foundation MCB-1553228
6 · The paper itself

Abstract

During embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent way. Yet, in mammalian embryos, concentrations change rapidly compared to the time for making cell fate decisions. Here, we use human embryonic stem cells (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. We show that BMP4 response is concentration dependent, but that expression of many Nodal targets depends on rate of concentration change. Moreover, in a self-organized stem cell model for human gastrulation, expression of these genes follows rapid changes in endogenous Nodal signaling. Our study shows a striking contrast between the specific ways ligand dynamics are interpreted by two closely related signaling pathways, highlighting both the subtlety and importance of morphogen dynamics for understanding mammalian embryogenesis and designing optimized protocols for directed stem cell differentiation. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Indexed as

Bone Morphogenetic Protein 4Cell DifferentiationCells, CulturedHuman Embryonic Stem CellsHumansNodal ProteinSignal TransductionBMP4 protein, humanBone Morphogenetic Protein 4Nodal ProteinNODAL protein, humanBMPcomputational biologydevelopmental biologyembryonic stem cellshumanmorphogennodalself-organizationsignaling dynamicssystems biology

Identifiers

PMID30829572
PMCPMC6398983
OpenAlexW2919475439

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.