Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities

Sisi Chen, Andrew W. Bremer, Olivia J. Scheideler, Yun Suk Na, Michael E. Todhunter, Sonny Hsiao, Prithvi R. Bomdica, Michel M. Maharbiz, Zev J. Gartner () and David V. Schaffer ()
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Sisi Chen: California Institute for Quantitative Biosciences, University of California, Berkeley
Andrew W. Bremer: University of California, Berkeley
Olivia J. Scheideler: University of California, Berkeley
Yun Suk Na: University of California, Berkeley
Michael E. Todhunter: University of California, San Francisco
Sonny Hsiao: Adheren
Prithvi R. Bomdica: University of California, Berkeley
Michel M. Maharbiz: The UC Berkeley—UCSF Graduate Program in Bioengineering, University of California, Berkeley
Zev J. Gartner: The UC Berkeley—UCSF Graduate Program in Bioengineering, University of California, Berkeley
David V. Schaffer: California Institute for Quantitative Biosciences, University of California, Berkeley

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10309

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