Self-organizing human cardiac microchambers mediated by geometric confinement

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

Research output: Contribution to journalArticle

54 Scopus citations

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.

Original languageEnglish (US)
Article number7413
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 14 2015
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Ma, Z., Wang, J., Loskill, P., Huebsch, N., Koo, S., Svedlund, F. L., Marks, N. C., Hua, E. W., Grigoropoulos, C. P., Conklin, B. R., & Healy, K. E. (2015). Self-organizing human cardiac microchambers mediated by geometric confinement. Nature Communications, 6, [7413]. https://doi.org/10.1038/ncomms8413