Journal article
Self-organizing circuitry and emergent computation in mouse embryonic stem cells
JD Halley, K Smith-Miles, DA Winkler, T Kalkan, S Huang, A Smith
Stem Cell Research | ELSEVIER SCIENCE BV | Published : 2012
Abstract
Pluripotency is a cellular state of multiple options. Here, we highlight the potential for self-organization to contribute to stem cell fate computation. A new way of considering regulatory circuitry is presented that describes the expression of each transcription factor (TF) as a branching process that propagates through time, interacting and competing with others. In a single cell, the interactions between multiple branching processes generate a collective process called 'critical-like self-organization'. We explain how this phenomenon provides a valid description of whole genome regulatory circuit dynamics. The hypothesis of exploratory stem cell decision-making proposes that critical-lik..
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Awarded by European Commission
Funding Acknowledgements
We thank Paul Sumption, Bruce Beckles, and Stephen Emmott and the Biological Computation Group at Microsoft Research Cambridge UK for discussion about coding concepts, Andrew Elefanty, Edouard Stanley, Elizabeth Ng, Brian Hendrich, Jose Silva, Paul Bertone, Nicola Reynolds, Elly Tanaka, Graziano Martello, Sabine Dietmann, Isabelle Nett, Sarah Teichmann and Martin Burd for other helpful discussions, and Alexey Gusev for Figure 1 and Kenneth Goldberg of Lawrence Berkeley National Laboratory for Figure 2. Special thanks go to Jennifer Nichols, Jason Wray, Davide Danovi and Jason Signolet for critical review of the manuscript, and to Business Victoria for a 2009 Victoria Fellowship, which enabled Dr Halley to travel to Canada and the UK where she met Professors Huang and Smith. This study was funded by the Medical Research Council and the European Commission Project EuroSystem.