Self-organizing human cardiac microchambers mediated by geometric confinement

Nat Commun. 2015 Jul 14;6:7413. doi: 10.1038/ncomms8413.

Abstract

Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial-mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Body Patterning
  • Cadherins
  • Cell Count
  • Cell Differentiation
  • Cell Lineage
  • Cell Movement
  • Cell Proliferation
  • Cues
  • Epithelial-Mesenchymal Transition*
  • Heart / embryology*
  • Humans
  • In Vitro Techniques
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Models, Cardiovascular
  • Morphogenesis*
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Myofibroblasts / cytology*
  • Myofibroblasts / metabolism
  • Stress, Mechanical*
  • Wnt Signaling Pathway

Substances

  • Cadherins