英国兰德尔细胞与分子生物物理中心Jody Rosenblatt研究团队揭示了能量缺乏选择拥挤的活上皮细胞进行挤压。相关论文于2025年9月10日发表在《自然》杂志上。

在这里，该课题组人员证明了能量和膜电位最小的拥挤细胞被选择用于提取。拥挤触发钠离子（Na⁺）通过上皮Na⁺通道（ENaC）进入细胞，使细胞去极化。当能量充足的细胞重新极化时，ATP有限的细胞继续去极化，这反过来又触发水通过电压门控钾（K⁺）通道Kv1.1和Kv1.2以及氯离子（Cl^-）SWELL1频道。瞬间失水引起细胞收缩，放大拥挤，激活拥挤诱导的活细胞外移。他们的研究结果表明，ENaC可以作为一种张力传感器，探测能量最小的细胞以挤压和死亡，可能会抑制背景细胞中Piezo1的无意拥挤激活。课题组揭示了Piezo1上游的拥挤感应机制，强调水调节和离子通道是上皮细胞更新的关键调节因子。

研究人员表示，上皮细胞共同提供保护屏障，但它们在细胞分裂和死亡过程中迅速翻转。如果分裂细胞和死亡细胞的数量不匹配，屏障就会消失，或者形成肿瘤。机械力通过拉伸激活的离子通道Piezo1连接这两个过程；拉伸促进细胞分裂，而拥挤则导致活细胞挤压然后死亡。然而，目前尚不清楚是什么选择了一个给定的拥挤细胞进行提取。

附：英文原文

Title: Energy deficiency selects crowded live epithelial cells for extrusion

Author: Mitchell, Saranne J., Pardo-Pastor, Carlos, Tchoumakova, Anastassia, Zangle, Thomas A., Rosenblatt, Jody

Issue&Volume: 2025-09-10

Abstract: Epithelial cells work collectively to provide a protective barrier, yet they turn over rapidly through cell division and death. If the numbers of dividing and dying cells do not match, the barrier can vanish, or tumours can form. Mechanical forces through the stretch-activated ion channel Piezo1 link both of the processes; stretch promotes cell division, whereas crowding triggers live cells to extrude and then die1,2. However, it was not clear what selects a given crowded cell for extrusion. Here we show that the crowded cells with the least energy and membrane potential are selected for extrusion. Crowding triggers sodium (Na+) entry through the epithelial Na+ channel (ENaC), which depolarizes cells. While those with sufficient energy repolarize, those with limited ATP remain depolarized, which, in turn, triggers water egress through the voltage-gated potassium (K+) channels Kv1.1 and Kv1.2 and the chloride (Cl) channel SWELL1. Transient water loss causes cell shrinkage, amplifying crowding to activate crowding-induced live cell extrusion. Thus, our findings suggest that ENaC acts as a tension sensor that probes for cells with the least energy to extrude and die, possibly damping inadvertent crowding activation of Piezo1 in background cells. We reveal crowding-sensing mechanisms upstream of Piezo1 that highlight water regulation and ion channels as key regulators of epithelial cell turnover.

DOI: 10.1038/s41586-025-09514-w

Source: https://www.nature.com/articles/s41586-025-09514-w