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Statistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions

Cornell Affiliated Author(s)

Author

M. Sáez
R. Blassberg
E. Camacho-Aguilar
E.D. Siggia
D.A. Rand
J. Briscoe

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. © 2021 The Author(s)

Date Published

Journal

Cell Systems

Volume

13

Issue

1

Number of Pages

12-28.e3,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123398237&doi=10.1016%2fj.cels.2021.08.013&partnerID=40&md5=37ae8b2dbbc9a6ce152aef55ee2474db

DOI

10.1016/j.cels.2021.08.013

Research Area

Funding Source

PHY-1748958
Phy 2013131
R25GM067110
2919.01
FC001051
1499350
EP/P019811/1
742138

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