Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering

Kim, Chloe S.; Yang, Xiaoqing; Jacobsen, S; Masters, Kristyn S.; Kreeger, Pamela K.

doi:10.1002/btm2.10138

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…While coordinated directionality refers to how cohesively cells migrate in a similar direction, directional persistence refers to the directed migration of individual cells or, more simply, how straight individual cell trajectories are. Notably, these two elements are often seen to co-occur in monolayers which show increased wound closure efficiency [ 46 ]. The directional persistence of a cell can be quantified by measuring the velocity autocorrelation of cell trajectories [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

Chen,

Holt,

Evans

et al. 2024

PLoS Comput Biol

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The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1’s contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration.

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Section: Resultsmentioning

confidence: 99%

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

Chen,

Holt,

Evans

et al. 2024

PLoS Comput Biol

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show abstract

“…While coordinated directionality refers to how cohesively cells migrate in a similar direction, directional persistence refers to the directed migration of individual cells or, more simply, how straight individual cell trajectories are. Notably, these two elements are often seen to co-occur in monolayers which show increased wound closure efficiency ( Kim et al (2019 )). The directional persistence of a cell can be quantified by measuring the velocity autocorrelation of cell trajectories ( Gorelik and Gautreau (2014 )).…”

Section: Resultsmentioning

confidence: 99%

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

Holt

Chen

Evans

et al. 2022

Preprint

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The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion as well as for the coordination of movement across cells. Leader cells initiated along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their uniform polarization and coordinated direction of migration, or directionality. Despite the observed importance of mechanical cues in leader cell formation and controlling directionality, the underlying biophysical mechanisms remain elusive. The mechanically activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds through retraction of keratinocytes located along the wound edge. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1's contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation along the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D-multiscale model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that directionality plays a key role during wound closure and is inhibited by PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits the coordination of directionality between cells during collective migration.

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“…We further analyzed the potential mechanism behind hADSC functions in SW-treated wounds. Previous literature has shown that wound repair is closely related to the EGF pathway [24], so we hypothesized that hADSCs induce proliferation and migration of wound repair The number and proportion of proliferating cells or skin stem cells in the control group and the SW+hADSC group were significantly higher than those in the SW group. Scale bars indicate 100 μm.…”

Section: Hadscs Affect Mek/erk Signaling Pathway Activationmentioning

confidence: 95%

Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

Xiong

Wang

et al. 2019

Stem Cells International

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Seawater (SW) immersion can increase the damage of skin wounds and produce refractory wounds. However, few studies have been conducted to investigate the mechanisms of SW immersion on skin wounds. In our current study, we investigated the effect of human adipose-derived stem cells (hADSCs) on the repair of SW-treated full-thickness skin wounds and the underlying mechanisms. The results showed that SW immersion could reduce the expression of EGF and suppress the activation of the MEK/ERK signaling pathway. At the same time, the proliferation and migration of skin stem cells were inhibited by SW immersion, resulting in delayed wound healing. However, hADSCs significantly accelerated the healing of SW-immersed skin wounds by promoting cell proliferation and migration through the aforementioned mechanisms. Our results indicate a role for hADSCs in the repair of seawater-immersed skin wounds and suggest a potential novel treatment strategy for seawater-immersed wound healing.

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Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering

Cited by 5 publications

References 36 publications

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration

Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

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