Single-cell intracellular pH dynamics regulate the cell cycle by timing the G1 exit and G2 transition

Area of Science:

• Cell Biology
• Biochemistry
• Physiology

Background:

• Transient changes in intracellular pH (pHi) regulate normal cell behaviors.
• The specific roles of spatiotemporal pHi dynamics in single-cell behaviors are not fully understood.

Purpose of the Study:

• To map single-cell spatiotemporal pHi dynamics during mammalian cell cycle progression.
• To investigate the influence of pHi on cell cycle phase transitions.

Main Methods:

• Mapping single-cell spatiotemporal pHi dynamics during cell cycle progression.
• Utilizing two independent methods to manipulate pHi.
• Observing effects of pHi manipulation on cell cycle phase transitions.

Main Results:

• Single-cell pHi exhibits dynamic changes throughout the cell cycle, with distinct patterns at G1/S, S, G2/M, and mitosis.
• Dividing cells show more dynamic pHi compared to non-dividing cells.
• Low pHi inhibits S phase completion, while high pHi promotes S/G2 and G2/M transitions.
• pHi levels influence G1 exit, G1 duration, and S phase timing.

Conclusions:

• Spatiotemporal pHi dynamics are essential for cell cycle progression at multiple phase transitions in single human cells.
• pHi acts as a critical regulator of cell cycle timing and progression.