Evidence map›Paper›PMID 28870989›Full record

ArticleDevelopment (Cambridge, England)2017

A stepwise model of reaction-diffusion and positional information governs self-organized human peri-gastrulation-like patterning.

Mukul Tewary, Joel Ostblom, Laura Prochazka, Teresa Zulueta-Coarasa, Nika Shakiba, Rodrigo Fernandez-Gonzalez, Peter W Zandstra

Open access · hybridAbstract read
In one paragraph

Article in Development (Cambridge, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
9.1field-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

84 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Pooled it
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  7. From genes to germ layers: virtual twins of gastruloids.NPJ systems biology and applications · 2026
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24 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.

Mukul TewaryInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Joel OstblomInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Laura ProchazkaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Teresa Zulueta-CoarasaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Nika ShakibaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Rodrigo Fernandez-GonzalezInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Peter W ZandstraInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario, M5S 3E1, Canada peter.zandstra@utoronto.ca.ORCID 0000-0002-9568-733X
University of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a reaction-diffusion (RD)-based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle. Consequent fate acquisition occurred as a function of both pSMAD1 signaling strength and duration of induction, consistent with the positional-information (PI) paradigm. We propose that the self-organized peri-gastrulation-like fate patterning in BMP4-treated geometrically confined hPSC colonies arises via a stepwise model of RD followed by PI. This two-step model predicted experimental responses to perturbations of key parameters such as colony size and BMP4 dose. Furthermore, it also predicted experimental conditions that resulted in RD-like periodic patterning in large hPSC colonies, and rescued peri-gastrulation-like patterning in colony sizes previously thought to be reticent to this behavior.

Indexed as

Models, BiologicalBody PatterningBone Morphogenetic Protein 4Carrier ProteinsCell DifferentiationCells, CulturedColony-Forming Units AssayGastrulationHigh-Throughput Screening AssaysHumansNodal ProteinNoggin ProteinPluripotent Stem CellsRNA, Small InterferingSignal TransductionSmad1 ProteinBMP4 protein, humanBone Morphogenetic Protein 4Carrier ProteinsNodal ProteinNODAL protein, humanNoggin ProteinRNA, Small InterferingSmad1 ProteinSMAD1 protein, humanDevelopmental organoidsHuman gastrulationMorphogenesisPluripotent stem cellsPositional informationReaction-diffusion

Identifiers

PMID28870989
PMCPMC5769627
OpenAlexW2751928832

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.