Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dynamics of actin polymerisation during the mammalian single-cell wound healing response.

ABSTRACT: OBJECTIVE:The contribution of actomyosin contractile rings in the wound healing program of somatic cells as never been directly assessed. This contrast with the events characterising the wound healing response of in wounded Xenopus oocytes, in which formation and contraction of an actomyosin ring provides a platform for cytoskeletal repair and drives the restoration of proper plasma membrane composition at the site of injury. As such, we aimed to characterize, using high-resolution live-cell confocal microscopy, the cytoskeletal repair dynamics of HeLa cells. RESULTS:We confirm here that the F-actin enrichment that characterizes the late repair program of laser-wounded cells is mostly uniform and is not associated with co-enrichment of myosin-II or the formation of concentric zones of RhoA and Cdc42 activity.

SUBMITTER: DeKraker C

PROVIDER: S-EPMC6636100 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dynamics of actin polymerisation during the mammalian single-cell wound healing response.

DeKraker Corina C Goldin-Blais Laurence L Boucher Eric E Mandato Craig A CA

BMC research notes 20190716 1

<h4>Objective</h4>The contribution of actomyosin contractile rings in the wound healing program of somatic cells as never been directly assessed. This contrast with the events characterising the wound healing response of in wounded Xenopus oocytes, in which formation and contraction of an actomyosin ring provides a platform for cytoskeletal repair and drives the restoration of proper plasma membrane composition at the site of injury. As such, we aimed to characterize, using high-resolution live- ...[more]

PMID: 31311589

Similar Datasets

Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.

Project description:Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence, the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately affect the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse's active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than nighttime wounds. We suggest that circadian regulation of the cytoskeleton influences wound-healing efficacy from the cellular to the organismal scale.

| S-EPMC5837001 | biostudies-literature

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing.

Project description:Mitochondria adapt to cellular needs by changes in morphology through fusion and fission events, referred to as mitochondrial dynamics. Mitochondrial function and morphology are intimately connected and the dysregulation of mitochondrial dynamics is linked to several human diseases. In this work, we investigated the role of mitochondrial dynamics in wound healing in the Drosophila embryonic epidermis. Mutants for mitochondrial fusion and fission proteins fail to close their wounds, indicating that the regulation of mitochondrial dynamics is required for wound healing. By live-imaging, we found that loss of function of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) compromises the increase of cytosolic and mitochondrial calcium upon wounding and leads to reduced reactive oxygen species (ROS) production and F-actin defects at the wound edge, culminating in wound healing impairment. Our results highlight a new role for mitochondrial dynamics in the regulation of calcium, ROS and F-actin during epithelial repair.

| S-EPMC7225088 | biostudies-literature

Two Septin complexes mediate actin dynamics during cell wound repair.

Project description:Cells have robust wound repair systems to prevent further damage or infection and to quickly restore cell cortex integrity when exposed to mechanical and chemical stress. Actomyosin ring formation and contraction at the wound edge are major events during closure of the plasma membrane and underlying cytoskeleton during cell wound repair. Here, we show that all five Drosophila Septins are required for efficient cell wound repair. Based on their different recruitment patterns and knockdown/mutant phenotypes, two distinct Septin complexes, Sep1/Sep2/Pnut and Sep4/Sep5/Pnut, are assembled to regulate actin ring assembly, contraction, and remodeling during the repair process. Intriguingly, we find that these two Septin complexes have different F-actin bending activities. In addition, we find that Anillin regulates the recruitment of only one of two Septin complexes upon wounding. Our results demonstrate that two functionally distinct Septin complexes work side by side to discretely regulate actomyosin ring dynamics during cell wound repair.

| S-EPMC11203717 | biostudies-literature

Bmi1+ Progenitor Cell Dynamics in Murine Cornea During Homeostasis and Wound Healing.

Project description:The outermost layer of the eye, the cornea, is renewed continuously throughout life. Stem cells of the corneal epithelium reside in the limbus at the corneal periphery and ensure homeostasis of the central epithelium. However, in young mice, homeostasis relies on cells located in the basal layer of the central corneal epithelium. Here, we first studied corneal growth during the transition from newborn to adult and assessed Keratin 19 (Krt19) expression as a hallmark of corneal maturation. Next, we set out to identify a novel marker of murine corneal epithelial progenitor cells before, during and after maturation, and we found that Bmi1 is expressed in the basal epithelium of the central cornea and limbus. Furthermore, we demonstrated that Bmi1+ cells participated in tissue replenishment in the central cornea. These Bmi1+ cells did not maintain homeostasis of the cornea for more than 3 months, reflecting their status as progenitor rather than stem cells. Finally, after injury, Bmi1+ cells fueled homeostatic maintenance, whereas wound closure occurred via epithelial reorganization. Stem Cells 2018;36:562-573.

| S-EPMC5929111 | biostudies-literature

Spatiotemporal dynamics of actin remodeling and endomembrane trafficking in alveolar epithelial type I cell wound healing.

Project description:Alveolar epithelial type I cell (ATI) wounding is prevalent in ventilator-injured lungs and likely contributes to pathogenesis of "barotrauma" and "biotrauma." In experimental models most wounded alveolar cells repair plasma membrane (PM) defects and survive insults. Considering the force balance between edge energy at the PM wound margins and adhesive interactions of the lipid bilayer with the underlying cytoskeleton (CSK), we tested the hypothesis that subcortical actin depolymerization is a key facilitator of PM repair. Using real-time fluorescence imaging of primary rat ATI transfected with a live cell actin-green fluorescent protein construct (Lifeact-GFP) and loaded with N-rhodamine phosphatidylethanolamine (PE), we examined the spatial and temporal coordination between cytoskeletal remodeling and PM repair following micropuncture. Membrane integrity was inferred from the fluorescence intensity profiles of the cytosolic label calcein AM. Wounding led to rapid depolymerization of the actin CSK near the wound site, concurrent with accumulation of endomembrane-derived N-rhodamine PE. Both responses were sustained until PM integrity was reestablished, which typically occurs between ?10 and 40 s after micropuncture. Only thereafter did the actin CSK near the wound begin to repolymerize, while the rate of endomembrane lipid accumulation decreased. Between 60 and 90 s after successful PM repair, after translocation of the actin nucleation factor cortactin, a dense actin fiber network formed. In cells that did not survive micropuncture injury, actin remodeling did not occur. These novel results highlight the importance of actin remodeling in ATI cell repair and suggest molecular targets for modulating the repair process.

| S-EPMC3075096 | biostudies-literature

Smooth muscle ? actin (Acta2) and myofibroblast function during hepatic wound healing.

Project description:Smooth muscle ? actin (Acta2) expression is largely restricted to smooth muscle cells, pericytes and specialized fibroblasts, known as myofibroblasts. Liver injury, associated with cirrhosis, induces transformation of resident hepatic stellate cells into liver specific myofibroblasts, also known as activated cells. Here, we have used in vitro and in vivo wound healing models to explore the functional role of Acta2 in this transformation. Acta2 was abundant in activated cells isolated from injured livers but was undetectable in quiescent cells isolated from normal livers. Both cellular motility and contraction were dramatically increased in injured liver cells, paralleled by an increase in Acta2 expression, when compared with quiescent cells. Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction. Additionally, Acta2 knockdown was associated with a significant reduction in Erk1/2 phosphorylation compared to control cells. The data indicate that Acta2 is important specifically in myofibroblast cell motility and contraction and raise the possibility that the Acta2 cytoskeleton, beyond its structural importance in the cell, could be important in regulating signaling processes during wound healing in vivo.

| S-EPMC3812165 | biostudies-literature

Defining stem cell dynamics and migration during wound healing in mouse skin epidermis.

Project description:Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here, we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. Functional experiments show that SC proliferation, migration and differentiation can be uncoupled during wound healing. Lineage tracing and quantitative clonal analysis reveal that, following wounding, progenitors divide more rapidly, but conserve their homoeostatic mode of division, leading to their rapid depletion, whereas SCs become active, giving rise to new progenitors that expand and repair the wound. These results have important implications for tissue regeneration, acute and chronic wound disorders.

| S-EPMC5339881 | biostudies-literature

cAMP Promotes Cell Migration Through Cell Junctional Complex Dynamics and Actin Cytoskeleton Remodeling: Implications in Skin Wound Healing.

Project description:Stem cells have attracted great interest for their therapeutic capacity in tissue regeneration. Cyclic adenosine 3',5'-monophosphate (cAMP), existing in high concentration at wound sites, mediated various signaling pathways such as cytoskeleton dynamics, cell adhesion, and cell migration in stem cells, which suggest the critical roles of cAMP in the wound healing process through functional regulation of stem cells. However, the mechanisms behind the effect of cAMP on mouse embryonic stem cell (mESC) motility and its roles on skin wound healing remain to be fully elucidated. In the present study, 8-Bromo cAMP-treated mESCs showed significant wound closure and improved neovascularization. Moreover, 8-Bromo cAMP stimulated mESC migration into the wound bed. 8-Bromo cAMP also increased ESC motility in in vitro migration assay. 8-Bromo cAMP induced myosin light chain phosphorylation through Rac1 and Cdc42 signaling, which were involved in 8-Bromo cAMP-induced decrease in expression of junction proteins (connexin 43, E-cadherin, and occludin) at the plasma membrane. Subsequently, 8-Bromo cAMP induced the disruption of cell junctions (including gap junctions, adherens junctions, and tight junctions), which reduced the function of the gap junctions and cell adhesion. In addition, 8-Bromo cAMP-induced Rac1 and Cdc42 activation increased Arp3, TOCA, PAK, and N-WASP expression, but decreased cofilin phosphorylation level, which elicited actin cytoskeleton remodeling. In contrast to the control, 8-Bromo cAMP evoked a substantial migration of cells into the denuded area, which was blocked by the small interfering RNAs of the signaling pathway-related molecules or by inhibitors. In conclusion, cAMP enhanced the migration of mESCs through effective coordination of junctional disruption and actin cytoskeleton remodeling, which increased the wound healing capacity of ESCs.

| S-EPMC4620535 | biostudies-other

Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics.

Project description:Our knowledge of transcriptional heterogeneities in epithelial stem and progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem and progenitor potential, but a comprehensive dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses predict a quasi-linear differentiation hierarchy where basal cells progress from Col17a1Hi/Trp63Hi state to early-response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal transcriptional states. Our study provides a systematic view of epidermal cellular dynamics, supporting a revised "hierarchical-lineage" model of homeostasis.

| S-EPMC7218802 | biostudies-literature

Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing.

Project description:Keratinocytes, the predominant cell type of the epidermis, migrate to reinstate the epithelial barrier during wound healing. Mechanical cues are known to regulate keratinocyte re-epithelialization and wound healing; however, the underlying molecular transducers and biophysical mechanisms remain elusive. Here, we show through molecular, cellular, and organismal studies that the mechanically activated ion channel PIEZO1 regulates keratinocyte migration and wound healing. Epidermal-specific Piezo1 knockout mice exhibited faster wound closure while gain-of-function mice displayed slower wound closure compared to littermate controls. By imaging the spatiotemporal localization dynamics of endogenous PIEZO1 channels, we find that channel enrichment at some regions of the wound edge induces a localized cellular retraction that slows keratinocyte collective migration. In migrating single keratinocytes, PIEZO1 is enriched at the rear of the cell, where maximal retraction occurs, and we find that chemical activation of PIEZO1 enhances retraction during single as well as collective migration. Our findings uncover novel molecular mechanisms underlying single and collective keratinocyte migration that may suggest a potential pharmacological target for wound treatment. More broadly, we show that nanoscale spatiotemporal dynamics of Piezo1 channels can control tissue-scale events, a finding with implications beyond wound healing to processes as diverse as development, homeostasis, disease, and repair.

| S-EPMC8577841 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data