Single-cell intracellular pH dynamics regulate the cell cycle by timing the G1 exit and G2 transition.
Single-cell intracellular pH dynamics regulate the cell cycle by timing the G1 exit and G2 transition.
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DOI：
10.1242/jcs.260458
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发表时间：
2023-05-15
影响因子：
4
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中科院分区：
文献类型：
--
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细胞内pH（pHi）的瞬时变化调节正常细胞的行为，但时空pHi动力学在单细胞行为中的作用仍不清楚。在这里，我们映射的单细胞时空pH值动态在哺乳动物细胞周期的进展与细胞周期同步。我们发现，单细胞pHi在整个细胞周期中是动态的：pHi在G1/S降低，在S中期增加，在S晚期降低，在G2/M增加，并在有丝分裂期间迅速降低。重要的是，尽管pHi在分裂细胞中是高度动态的，但非分裂细胞具有减弱的pHi动态。使用两种独立的pHi操作方法，我们发现低pHi抑制S期的完成，而高pHi促进S/G2和G2/M转换。我们的数据还表明，低pHi提示G1退出，减少pHi缩短G1和增加pHi延长G1。此外，S相定时需要动态pHi，因为高pHi延长S相并且低pHi抑制S/G2转变。这项工作表明，时空pHi动力学是必要的细胞周期进程在多个阶段的转变，在单一的人类细胞。 单细胞胞内pH值（pHi）的测量揭示了哺乳动物细胞周期中的振荡。操纵pHi改变相位长度和转换，表明pHi动力学调节细胞周期。
Transient changes in intracellular pH (pHi) regulate normal cell behaviors, but roles for spatiotemporal pHi dynamics in single-cell behaviors remain unclear. Here, we mapped single-cell spatiotemporal pHi dynamics during mammalian cell cycle progression both with and without cell cycle synchronization. We found that single-cell pHi is dynamic throughout the cell cycle: pHi decreases at G1/S, increases in mid-S, decreases at late S, increases at G2/M and rapidly decreases during mitosis. Importantly, although pHi is highly dynamic in dividing cells, non-dividing cells have attenuated pHi dynamics. Using two independent pHi manipulation methods, we found that low pHi inhibits completion of S phase whereas high pHi promotes both S/G2 and G2/M transitions. Our data also suggest that low pHi cues G1 exit, with decreased pHi shortening G1 and increased pHi elongating G1. Furthermore, dynamic pHi is required for S phase timing, as high pHi elongates S phase and low pHi inhibits S/G2 transition. This work reveals that spatiotemporal pHi dynamics are necessary for cell cycle progression at multiple phase transitions in single human cells. Single-cell intracellular pH (pHi) measurements reveal oscillations during the mammalian cell cycle. Manipulating pHi alters phase lengths and transitions, suggesting pHi dynamics regulate the cell cycle.
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影响因子：
5.2
作者：
Czowski BJ;Romero-Moreno R;Trull KJ;White KA
通讯作者：
White KA
影响因子：
4.3
作者：
Grant, Gavin D.;Kedziora, Katarzyna M.;Purvis, Jeremy E.
通讯作者：
Purvis, Jeremy E.
影响因子：
15
作者：
Donahue CET;Siroky MD;White KA
通讯作者：
White KA
影响因子：
3.5
作者：
Bolderson, E;Scorah, J;Meuth, M
通讯作者：
Meuth, M
影响因子：
64.5
作者：
AERTS, RJ;DURSTON, AJ;MOOLENAAR, WH
通讯作者：
MOOLENAAR, WH