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.
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|California Institute for Quantitative Biosciences, Berkeley, California 94720, USA.|Department of Material Science and Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|California Institute for Quantitative Biosciences, Berkeley, California 94720, USA.|Department of Material Science and Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Loskill
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California 94143, USA.|Department of Medicine, University of California, San Francisco, California 94143, USA.|Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.affiliation: Department of Mechanical Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Sangmo
authors.initials: S
authors.lastname: Koo
authors.affiliation: Department of Material Science and Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Svedlund
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Marks
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California 94143, USA.
authors.forename: Ethan W
authors.initials: EW
authors.lastname: Hua
authors.affiliation: Department of Mechanical Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Costas P
authors.initials: CP
authors.lastname: Grigoropoulos
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California 94143, USA.|Department of Medicine, University of California, San Francisco, California 94143, USA.|Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Conklin
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|California Institute for Quantitative Biosciences, Berkeley, California 94720, USA.|Department of Material Science and Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Healy
mesh_terms: D019521:Body Patterning; D015820:Cadherins; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D003463:Cues; D058750:Epithelial-Mesenchymal Transition; D006321:Heart / Q000196:embryology*; D006801:Humans; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008955:Models, Cardiovascular; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D013314:Stress, Mechanical; D060449:Wnt Signaling Pathway
chemical_list: D015820:Cadherins