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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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Updated: Jan 28, 2026

Patterning the Geometry of Human Embryonic Stem Cell Colonies on Compliant Substrates to Control Tissue-Level Mechanics
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Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells.

Idse Heemskerk1, Kari Burt1, Matthew Miller1

  • 1Department of Biosciences, Rice University, Houston, United States.

Elife
|March 5, 2019
PubMed
Summary
This summary is machine-generated.

Morphogen signaling in human embryonic stem cells (hESCs) reveals distinct pathway responses. BMP4 signaling depends on concentration, while Nodal signaling responds to the rate of change, impacting gastrulation.

Keywords:
BMPcomputational biologydevelopmental biologyembryonic stem cellshumanmorphogennodalself-organizationsignaling dynamicssystems biology

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Biochemistry

Background:

  • Morphogens are crucial signaling molecules in embryonic development, traditionally thought to act in a concentration-dependent manner to determine cell fates.
  • Mammalian embryonic development involves rapid changes in morphogen concentrations, posing a challenge to simple concentration-dependent models.
  • Understanding how cells interpret dynamic signaling is key to deciphering developmental processes and improving stem cell differentiation protocols.

Purpose of the Study:

  • To investigate how dynamic changes in morphogen levels influence cell fate decisions during human embryonic development.
  • To differentiate the roles of BMP4 and Nodal signaling pathways in governing cell fate during gastrulation using human embryonic stem cells (hESCs).
  • To explore the interpretation of ligand dynamics by closely related signaling pathways.

Main Methods:

  • Utilized human embryonic stem cells (hESCs) as a model system.
  • Analyzed the concentration-dependent response to BMP4 signaling.
  • Investigated the dependence of Nodal target gene expression on the rate of concentration change.
  • Employed a self-organized stem cell model for human gastrulation to study endogenous Nodal signaling dynamics.

Main Results:

  • BMP4 signaling response was found to be concentration-dependent.
  • Expression of numerous Nodal target genes was dependent on the rate of change in Nodal concentration, not just the absolute level.
  • In a human gastrulation model, target gene expression accurately reflected rapid fluctuations in endogenous Nodal signaling.
  • Demonstrated contrasting mechanisms by which BMP4 and Nodal pathways interpret ligand dynamics.

Conclusions:

  • Cell fate decisions in mammalian embryogenesis are influenced by the dynamics of morphogen signaling, not solely by static concentrations.
  • The Nodal signaling pathway interprets ligand dynamics by responding to the rate of concentration change, a mechanism distinct from BMP4's concentration-dependent response.
  • These findings highlight the importance of morphogen dynamics in mammalian embryogenesis and offer insights for optimizing directed stem cell differentiation protocols.