@article{cabc04b0a62448b6ba4a3dca9f31c675,
title = "Self-organizing human cardiac microchambers mediated by geometric confinement",
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.",
author = "Zhen Ma and Jason Wang and Peter Loskill and Nathaniel Huebsch and Sangmo Koo and Svedlund, {Felicia L.} and Marks, {Natalie C.} and Hua, {Ethan W.} and Grigoropoulos, {Costas P.} and Conklin, {Bruce R.} and Healy, {Kevin E.}",
note = "Funding Information: This work was supported by NIH-NIBIB R21EB021003, NIH-NHLBI R01HL096525, R01HL108677, U01HL100406 and U01HL098179, and in part by NIH-NCATS UH2TR000487 and UH3TR000487. N.H. acknowledges support from NIH T32 HL007544. We acknowledge assistance from the Berkeley Stem Cell Shared Facility for time-lapse microscopy, the Biological Imaging Facility for confocal microscopy and the Biomolecular Nanotechnology Center for scanning electron microscopy. For surface characterization (XPS and ToF-SIMS), we acknowledge the National ESCA and Surface Analysis Center (NESAC/BIO) at the University of Washington, Seattle supported by NIBIB grant EB-002027. We acknowledge Professor Charles D. Little from the University of Kansas Medical Center for his insightful discussions regarding the developmental process of the human heart. We acknowledge Micaela A. Finnegan for her help on hiPSC culturing and qRT–PCR analysis. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jul,
day = "14",
doi = "10.1038/ncomms8413",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}