空间限域诱导表皮角质形成细胞振荡迁移，形成具有EMT动态的三区室上皮结构
Spatial confinement induces oscillatory migration of epidermal keratinocytes and forms a three-compartment epithelial structure with epithelial–mesenchymal transition dynamics
角质形成细胞在3.0 µm微孔膜上迁移时形成由原上皮、EMT状态细胞和MET后新上皮组成的三区室结构，而孔径更大的膜无法维持该结构。活细胞成像显示，细胞以振荡方式运动，富肌动蛋白的丝状伪足样结构反复伸入和退出3.0 µm微孔，在较大微孔中则单向迁移。Piezo1和keratin 6被鉴定为细胞进出3.0 µm微孔的负向调控因子。结果表明，非癌性上皮细胞可通过限域空间以振荡方式迁移，这可能参与再现伤口愈合关键特征的三区室上皮结构形成。
来源：eLife · doi.org
Epithelial cells undergo epithelial–mesenchymal transition (EMT) during migration and regain their epithelial phenotype in the post-migration phase (mesenchymal–epithelial transition [MET]). We established an experimental system that reproduces a three-compartment epithelial structure comprising the original epithelium, its EMT state, and its MET state. Keratinocytes (KCs), skin epithelial cells, placed on a microporous membrane, migrated through 3.0 µm or larger micropores. The 3.0-µm-pored membrane induced an epithelial structure with three distinct states: stratified KCs above the membrane, KCs showing EMT within the micropores, and a new stratified epithelium under the membrane. The membrane with larger micropores failed to maintain the three-compartment epithelial structure. Live imaging revealed that KCs moved in an oscillatory manner, with actin-rich filopodia-like structures extending into and out of the 3.0 µm micropores, while the cells migrated unidirectionally into larger micropores. Piezo1 and keratin 6 were identified as negative modulators of KC entry into and exit from the 3.0 µm micropores. These results demonstrate that non-cancerous epithelial cells migrate through confined spaces in an oscillatory manner, which might contribute to the formation of a three-compartment epithelial structure that recapitulates key aspects of wound healing.