Monitoring single-cell dynamics of entry into quiescence during an unperturbed life cycle

eLife

Théo Aspert¹  Gilles Charvin¹  Basile Jacquel¹  Isabelle Sagot²  Damien Laporte² 

[1] Department of Developmental Biology and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France;Centre National de la Recherche Scientifique, Illkirch, France;Institut National de la Santé et de la Recherche Médicale, Illkirch, France;Université de Strasbourg, Illkirch, France;Institut de Biochimie et Génétique Cellulaires, UMR 5095 CNRS - Université de Bordeaux, Bordeaux, France, Bordeaux, France;

关键词: quiescence;    microfluidics;    single-cell dynamics;    cytosolic pH;    S. cerevisiae;   

DOI  :  10.7554/eLife.73186

来源: eLife Sciences Publications, Ltd

【 摘 要 】

The life cycle of microorganisms is associated with dynamic metabolic transitions and complex cellular responses. In yeast, how metabolic signals control the progressive choreography of structural reorganizations observed in quiescent cells during a natural life cycle remains unclear. We have developed an integrated microfluidic device to address this question, enabling continuous single-cell tracking in a batch culture experiencing unperturbed nutrient exhaustion to unravel the coordination between metabolic and structural transitions within cells. Our technique reveals an abrupt fate divergence in the population, whereby a fraction of cells is unable to transition to respiratory metabolism and undergoes a reversible entry into a quiescence-like state leading to premature cell death. Further observations reveal that nonmonotonous internal pH fluctuations in respiration-competent cells orchestrate the successive waves of protein superassemblies formation that accompany the entry into a bona fide quiescent state. This ultimately leads to an abrupt cytosolic glass transition that occurs stochastically long after proliferation cessation. This new experimental framework provides a unique way to track single-cell fate dynamics over a long timescale in a population of cells that continuously modify their ecological niche.

【 授权许可】

CC BY