Integration of Multiple Metabolic Signals Determines Cell Fate Prior to Commitment

Molecular Cell
Orlando Argüello-MirandaAndreas Doncic

Abstract

Cell-fate decisions are central to the survival and development of both uni- and multicellular organisms. It remains unclear when and to what degree cells can decide on future fates prior to commitment. This uncertainty stems from experimental and theoretical limitations in measuring and integrating multiple signals at the single-cell level during a decision process. Here, we combine six-color live-cell imaging with the Bayesian method of statistical evidence to study the meiosis/quiescence decision in budding yeast. Integration of multiple upstream metabolic signals predicts individual cell fates with high probability well before commitment. Cells "decide" their fates before birth, well before the activation of pathways characteristic of downstream cell fates. This decision, which remains stable through several cell cycles, occurs when multiple metabolic parameters simultaneously cross cell-fate-specific thresholds. Taken together, our results show that cells can decide their future fates long before commitment mechanisms are activated.

Citations

Jul 18, 2019·Communications Biology·Nicholas A RossiMary J Dunlop
May 10, 2020·Nature Communications·Janis Tam, Folkert J van Werven
Jan 4, 2019·Journal of Cell Science·Isabelle Sagot, Damien Laporte
Jan 17, 2019·Current Genetics·Isabelle Sagot, Damien Laporte
Jan 15, 2021·Scientific Reports·Lisa DenglerJennifer C Ewald
Dec 23, 2020·Yeast·Siyu Sun, David Gresham
Jan 12, 2020·Communications Biology·Nicholas A RossiMary J Dunlop
Nov 20, 2020·Experimental Cell Research·Kristopher MontroseJuha Saarikangas
Mar 21, 2021·Applied and Environmental Microbiology·Taylor ReiterBen Montpetit
Jun 18, 2021·Cell Systems·Mojca Mattiazzi UsajBrenda J Andrews
Oct 26, 2021·The Journal of Cell Biology·Orlando Argüello-MirandaJungsik Noh
Nov 25, 2021·Molecular Biology of the Cell·Mehmet Oguz GokJonathan R Friedman

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