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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Astrocytes
  • Calcium-Binding Proteins
  • Cell Communication*
  • Cell Differentiation
  • Cell Line
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism*
  • HEK293 Cells
  • High-Throughput Screening Assays
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neural Stem Cells / metabolism*
  • Paracrine Communication*
  • Phenotype
  • Rats
  • Time-Lapse Imaging
  • Tissue Array Analysis

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • EFNB2 protein, human
  • Ephrin-B2
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins