title: Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities.
abstract: Recreating heterotypic cell-cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell-cell signalling networks, we prepared heterotypic cell-cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals.
authors.affiliation: California Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA.
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bremer
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Olivia J
authors.initials: OJ
authors.lastname: Scheideler
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Na
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.|Tetrad Graduate Program, University of California, San Francisco, California 94158, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Todhunter
authors.affiliation: Adheren, Emeryville, California 94662, USA.
authors.forename: Sonny
authors.initials: S
authors.lastname: Hsiao
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Prithvi R
authors.initials: PR
authors.lastname: Bomdica
authors.affiliation: The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Electrical Engineering, University of California, Berkeley, California 94720, USA.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Maharbiz
authors.affiliation: The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.|Tetrad Graduate Program, University of California, San Francisco, California 94158, USA.|Center for Systems and Synthetic Biology, University of California, San Francisco, California 94158, USA.|Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, California 94158, USA.
authors.forename: Zev J
authors.initials: ZJ
authors.lastname: Gartner
authors.affiliation: California Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA.|Department of Bioengineering, University of California, Berkeley, California 94720, USA.|The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Chemical Engineering, University of California, Berkeley, California 94720, USA.|Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D001253:Astrocytes; D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002454:Cell Differentiation; D002460:Cell Line; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D019899:Paracrine Communication; D010641:Phenotype; D051381:Rats; D059008:Time-Lapse Imaging; D046888:Tissue Array Analysis
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C000601239:EFNB2 protein, human; D036388:Ephrin-B2; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins