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Statistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions
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Sáez, Meritxell, Blassberg, Robert, Camacho-Aguilar, Elena, Siggia, Eric D., Rand, David A. and Briscoe, James (2022) Statistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions. Cell Systems, 13 (1). pp. 12-28. doi:10.1016/j.cels.2021.08.013
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Official URL: http://dx.doi.org/10.1016/j.cels.2021.08.013
Abstract
Fate decisions in developing tissues involve cells transitioning between discrete cell states, each defined by distinct gene expression profiles. The Waddington landscape, in which the development of a cell is viewed as a ball rolling through a valley filled terrain, is an appealing way to describe differentiation. To construct and validate accurate landscapes, quantitative methods based on experimental data are necessary. We combined principled statistical methods with a framework based on catastrophe theory and approximate Bayesian computation to formulate a quantitative dynamical landscape that accurately predicts cell fate outcomes of pluripotent stem cells exposed to different combinations of signaling factors. Analysis of the landscape revealed two distinct ways in which cells make a binary choice between one of two fates. We suggest that these represent archetypal designs for developmental decisions. The approach is broadly applicable for the quantitative analysis of differentiation and for determining the logic of developmental decisions.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history | ||||||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Gene expression , Gene expression -- Statistical methods, Cells -- Growth -- Mathematical models | ||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Cell Systems | ||||||||||||||||||||||||||||||||||||
| Publisher: | Cell Press | ||||||||||||||||||||||||||||||||||||
| ISSN: | 2405-4712 | ||||||||||||||||||||||||||||||||||||
| Official Date: | 19 January 2022 | ||||||||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 13 | ||||||||||||||||||||||||||||||||||||
| Number: | 1 | ||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 12-28 | ||||||||||||||||||||||||||||||||||||
| DOI: | 10.1016/j.cels.2021.08.013 | ||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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