Authors:
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
Summary:
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.
Source:
Nature Communications; 6, 7413 (07/14/15)