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Nat Commun. 2016 Jan 12;7:10309. doi: 10.1038/ncomms10309.

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

Author information

1
California Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA.
2
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
3
The UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, California 94720, USA.
4
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
5
Tetrad Graduate Program, University of California, San Francisco, California 94158, USA.
6
Adheren, Emeryville, California 94662, USA.
7
Department of Electrical Engineering, University of California, Berkeley, California 94720, USA.
8
Center for Systems and Synthetic Biology, University of California, San Francisco, California 94158, USA.
9
Chemistry &Chemical Biology Graduate Program, University of California, San Francisco, California 94158, USA.
10
Department of Chemical Engineering, University of California, Berkeley, California 94720, USA.
11
Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.

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.

PMID:
26754526
PMCID:
PMC4729920
DOI:
10.1038/ncomms10309
[Indexed for MEDLINE]
Free PMC Article

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