Evidence map›Paper›PMID 27452175›Full record

ArticleCell stem cell2016

Tissue Mechanics Orchestrate Wnt-Dependent Human Embryonic Stem Cell Differentiation.

Laralynne Przybyla, Johnathon N Lakins, Valerie M Weaver

Abstract read
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
11.4field-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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026
    Review
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  18. Article
  19. Primate amnion development.Development (Cambridge, England) · 2024
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Laralynne PrzybylaCenter for Bioengineering and Tissue Regeneration and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Johnathon N LakinsCenter for Bioengineering and Tissue Regeneration and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Valerie M WeaverCenter for Bioengineering and Tissue Regeneration and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Departments of Anatomy, Bioengineering, and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and The Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: valerie.weaver@ucsf.edu.
University of California, San Francisco · USBroad Center · US

Funding

ECM geometrical and mechanical properties modulate RTK signalingU01CA202241 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI GROVES, JAY T., WEAVER, VALERIE MARIE · 2015 to 2019
$3.3M
Tension-Stat3-miR-mediated metastasisR01CA192914 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEEWALDT, VICTORIA L., WEAVER, VALERIE MARIE · 2015 to 2019
$2.9M
NCI NIH HHS R01 CA192914NCI NIH HHS U01 CA202241
6 · The paper itself

Abstract

Regenerative medicine is predicated on understanding the mechanisms regulating development and applying these conditions to direct stem cell fate. Embryogenesis is guided by cell-cell and cell-matrix interactions, but it is unclear how these physical cues influence stem cells in culture. We used human embryonic stem cells (hESCs) to examine whether mechanical features of the extracellular microenvironment could differentially modulate mesoderm specification. We found that, on a hydrogel-based compliant matrix, hESCs accumulate β-catenin at cell-cell adhesions and show enhanced Wnt-dependent mesoderm differentiation. Mechanistically, Src-driven ubiquitination of E-cadherin by Cbl-like ubiquitin ligase releases P120-catenin to facilitate transcriptional activity of β-catenin, which initiates and reinforces mesoderm differentiation. By contrast, on a stiff hydrogel matrix, hESCs show elevated integrin-dependent GSK3 and Src activity that promotes β-catenin degradation and inhibits differentiation. Thus, we found that mechanical features of the microenvironmental matrix influence tissue-specific differentiation of hESCs by altering the cellular response to morphogens.

Indexed as

Cell DifferentiationAdherens JunctionsAnimalsbeta CateninBiomechanical PhenomenaCadherinsCell LineCell Self RenewalChick EmbryoEpithelial-Mesenchymal TransitionExtracellular MatrixHuman Embryonic Stem CellsHumansMesodermMicesrc-Family Kinasesbeta CateninCadherinssrc-Family KinasesWnt Proteins

Identifiers

PMID27452175
PMCPMC5336327
OpenAlexW2501380663

What OpenQuestion holds

Textmetadata
LicenceTDM
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.