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Self-organizing human cardiac microchambers mediated by geometric confinement

Author

Listed:
  • Zhen Ma

    (University of California
    California Institute for Quantitative Biosciences
    University of California)

  • Jason Wang

    (University of California)

  • Peter Loskill

    (University of California
    California Institute for Quantitative Biosciences
    University of California)

  • Nathaniel Huebsch

    (Gladstone Institute of Cardiovascular Disease
    University of California
    University of California)

  • Sangmo Koo

    (University of California)

  • Felicia L. Svedlund

    (University of California)

  • Natalie C. Marks

    (University of California)

  • Ethan W. Hua

    (Gladstone Institute of Cardiovascular Disease)

  • Costas P. Grigoropoulos

    (University of California)

  • Bruce R. Conklin

    (Gladstone Institute of Cardiovascular Disease
    University of California
    University of California)

  • Kevin E. Healy

    (University of California
    California Institute for Quantitative Biosciences
    University of California)

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.

Suggested Citation

  • Zhen Ma & Jason Wang & Peter Loskill & Nathaniel Huebsch & Sangmo Koo & Felicia L. Svedlund & Natalie C. Marks & Ethan W. Hua & Costas P. Grigoropoulos & Bruce R. Conklin & Kevin E. Healy, 2015. "Self-organizing human cardiac microchambers mediated by geometric confinement," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8413
    DOI: 10.1038/ncomms8413
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