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

Self-organizing human cardiac microchambers mediated by geometric confinement.

Author information

1
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
2
California Institute for Quantitative Biosciences, Berkeley, California 94720, USA.
3
Department of Material Science and Engineering, University of California, Berkeley, California 94720, USA.
4
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94143, USA.
5
Department of Medicine, University of California, San Francisco, California 94143, USA.
6
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
7
Department of Mechanical Engineering, University of California, Berkeley, California 94720, USA.

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.

PMID:
26172574
PMCID:
PMC4503387
DOI:
10.1038/ncomms8413
[Indexed for MEDLINE]
Free PMC Article

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