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Author Notes:

Correspondence and requests for materials should be addressed to T.C.M. (email: todd.mcdevitt@gladstone.ucsf.edu) or to M.L.K. (email: melissa.kemp@bme.gatech.edu)

Model development, data acquisition and analysis: C.M.G.

Study design, interpretation of data, and writing of the manuscript: C.M.G, T.C.M., M.L.K.

The authors gratefully acknowledge assistance in confocal imaging from Dr. Aaron Lifland and Andrew Shaw in the Parker H. Petit Institute Optical Microscopy Core.

The authors declare no competing interests.

Subjects:

Research Funding:

The authors gratefully acknowledge funding to M.L.K. and T.C.M. from NSF Emergent Behaviors of Integrated Cellular Systems Science and Technology Center (CBET 0939511), and a graduate research fellowship to C.M.G. from the Natural Sciences and Engineering Research Council of Canada.

Keywords:

  • computational modeling
  • dynamic networks
  • multicellular systems
  • pattern formation
  • stem-cell differentiation
  • neural commitment

Dynamic intercellular transport modulates the spatial patterning of differentiation during early neural commitment.

Journal Title:

Nature Communications

Volume:

Volume 9, Number 1

Publisher:

, Pages 4111-4111

Type of Work:

Article | Final Publisher PDF

Abstract:

The initiation of heterogeneity within a population of phenotypically identical progenitors is a critical event for the onset of morphogenesis and differentiation patterning. Gap junction communication within multicellular systems produces complex networks of intercellular connectivity that result in heterogeneous distributions of intracellular signaling molecules. In this study, we investigate emergent systems-level behavior of the intercellular network within embryonic stem cell (ESC) populations and corresponding spatial organization during early neural differentiation. An agent-based model incorporates experimentally-determined parameters to yield complex transport networks for delivery of pro-differentiation cues between neighboring cells, reproducing the morphogenic trajectories during retinoic acid-accelerated mouse ESC differentiation. Furthermore, the model correctly predicts the delayed differentiation and preserved spatial features of the morphogenic trajectory that occurs in response to intercellular perturbation. These findings suggest an integral role of gap junction communication in the temporal coordination of emergent patterning during early differentiation and neural commitment of pluripotent stem cells.

Copyright information:

© The Author(s) 2018

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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