title: 3D niche microarrays for systems-level analyses of cell fate.
abstract: The behaviour of mammalian cells in a tissue is governed by the three-dimensional (3D) microenvironment and involves a dynamic interplay between biochemical and mechanical signals provided by the extracellular matrix (ECM), cell-cell interactions and soluble factors. The complexity of the microenvironment and the context-dependent cell responses that arise from these interactions have posed a major challenge to understanding the underlying regulatory mechanisms. Here we develop an experimental paradigm to dissect the role of various interacting factors by simultaneously synthesizing more than 1,000 unique microenvironments with robotic nanolitre liquid-dispensing technology and by probing their effects on cell fate. Using this novel 3D microarray platform, we assess the combined effects of matrix elasticity, proteolytic degradability and three distinct classes of signalling proteins on mouse embryonic stem cells, unveiling a comprehensive map of interactions involved in regulating self-renewal. This approach is broadly applicable to gain a systems-level understanding of multifactorial 3D cell-matrix interactions.
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Ranga
authors.affiliation: 1] Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland [2].
authors.forename: S
authors.initials: S
authors.lastname: Gobaa
authors.affiliation: 1] Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland [2].
authors.forename: Y
authors.initials: Y
authors.lastname: Okawa
authors.affiliation: 1] Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland [2].
authors.forename: K
authors.initials: K
authors.lastname: Mosiewicz
authors.affiliation: 1] Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland [2].
authors.forename: A
authors.initials: A
authors.lastname: Negro
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
authors.forename: M P
authors.initials: MP
authors.lastname: Lutolf
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D005109:Extracellular Matrix; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D051379:Mice; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate