Heritable stress response dynamics revealed by single-cell genealogy

Area of Science:

• Cellular biology
• Genetics
• Biophysics

Background:

• Cells respond to environmental changes by activating transcription factors.
• In yeast (Saccharomyces cerevisiae), glucose limitation stress causes Msn2 dephosphorylation, nuclear localization, and gene activation.
• The dynamics and inheritance of Msn2 nucleocytoplasmic translocations under stress are not fully understood.

Purpose of the Study:

• To investigate how yeast cells modulate Msn2 nuclear localization dynamics in response to glucose limitation.
• To determine if these Msn2 localization dynamics are inherited across generations.
• To understand the evolutionary implications of stress response dynamics.

Main Methods:

• Tracking Msn2 localization events in yeast lineages using microfluidic chips.
• Analyzing amplitude, duration, frequency, and dynamic patterns of Msn2 translocation.
• Employing information theory to assess pattern similarity in genealogically related cells.

Main Results:

• Yeast cells modulate Msn2 nuclear localization amplitude and frequency, but not duration.
• Msn2 localization frequency is epigenetically inherited, reducing cell-to-cell variation.
• Pattern similarity of Msn2 localization increases with stress intensity and is strongly inherited.

Conclusions:

• Yeast cells exhibit adaptive modulation of Msn2 dynamics in response to stress.
• Epigenetic inheritance of Msn2 localization patterns contributes to population homogeneity under stress.
• Understanding these dynamics offers insights into evolutionary strategies for optimizing fitness in stressful environments.