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| Open AccessFocal adhesions contain three specialized actin nanoscale layers
Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.
- Reena Kumari
- , Katharina Ven
- & Pekka Lappalainen
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Article
| Open AccessCanonical and non-canonical integrin-based adhesions dynamically interconvert
Cells employ integrin-based adhesions with different molecular compositions to adhere to substrates. Here, the authors show that so-called “non-canonical” adhesions lacking focal adhesion components can convert to focal adhesions (and vice versa), through the selective exchange of components.
- Fabian Lukas
- , Claudia Matthaeus
- & Tanja Maritzen
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Article
| Open AccessEndothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts
During alveologenesis myofibroblasts contractions at terminal sacs produce alveoli in the lungs. Here they show that endothelial cells promote myofibroblast-driven alveologenesis by forming basement membranes via Rap1-induced integrin β1 activation.
- Haruko Watanabe-Takano
- , Katsuhiro Kato
- & Shigetomo Fukuhara
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Article
| Open AccessJAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development
The authors identified a cell population in Drosophila follicles that elaborate filopodia penetrating the oocyte they are contacting. These somatic cells are essential during oogenesis to regulate polarity and germline development of the future embryo.
- Charlotte Mallart
- , Sophie Netter
- & Marianne Malartre
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Article
| Open AccessGenome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover
Mechanisms regulating collagen clearance may be useful for treating fibrosis. Here, the authors conducted functional genome-wide screens and found that collagen biosynthesis directly regulates collagen clearance via a noncanonical function of SEL1L.
- Michael J. Podolsky
- , Benjamin Kheyfets
- & Kamran Atabai
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Article
| Open AccessN2FXm, a method for joint nuclear and cytoplasmic volume measurements, unravels the osmo-mechanical regulation of nuclear volume in mammalian cells
Cells exert tight control over the size of their compartments in order to regulate their function. Here, nuclear fluorescence exclusion microscopy is able to measure the nuclear and cytoplasmic volumes of live cells in a high-throughput way.
- Fabrizio A. Pennacchio
- , Alessandro Poli
- & Paolo Maiuri
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Article
| Open AccessExpression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells
The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been associated with primary biliary cholangitis. Here, the authors demonstrate that CD8+ T cells invade BEC using a mechanism that is dependent on cytoskeletal rearrangements and E-cadherin:β-catenin interactions.
- Scott P. Davies
- , Vincenzo Ronca
- & Ye H. Oo
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Article
| Open AccessLFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity
CD8+ T cell activation involves cooperation between the T cell receptor and the integrin LFA-1. Here authors show how LFA-1 nanoclusters participate in the calibration of TCR stimulation strength and activation of cytotoxic function in CD8+ T cells.
- Claire Lacouture
- , Beatriz Chaves
- & Loïc Dupré
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Article
| Open AccessLongevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans
Mechanotransduction can be defined as translating physical forces into gene expression, which subsequently drives cell fate. Here, Teuscher et al. showed that mechanotransduction across multiple tissues and extracellular matrices is essential for promoting longevity in vivo.
- Alina C. Teuscher
- , Cyril Statzer
- & Collin Y. Ewald
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Article
| Open AccessHuman apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation
Airway organoids made in Matrigel are in basal-out orientation. Here, authors present apical-out nasal organoids using a biochemically defined hydrogel system, revealing that matrix metalloproteinases are required for normal epithelial development.
- Liyue Li
- , Linyi Jiao
- & Chunwei Li
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Article
| Open AccessForce transmission by retrograde actin flow-induced dynamic molecular stretching of Talin
Focal adhesion proteins transmit intracellular forces to the extracellular matrix (ECM). Here, the authors show a force transmission by elastic transient clutch of Talin between ECM and constantly flowing F-actin at focal adhesions.
- Sawako Yamashiro
- , David M. Rutkowski
- & Naoki Watanabe
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Article
| Open AccessMolecular basis and cellular functions of vinculin-actin directional catch bonding
This study provides insights into the directional catch bonding of the linker protein vinculin by elucidating the molecular basis of mechanical reinforcement as well as unveiling its key role in subcellular organization and cellular processes.
- Venkat R. Chirasani
- , Mohammad Ashhar I. Khan
- & Sharon L. Campbell
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Article
| Open AccessIntracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Biosensors so far have mostly reported external traction forces exerted against the extracellular matrix or within adhesion receptors. Here, the authors present a sensor that reports molecular tension within the F-actin cytoskeleton.
- Sorosh Amiri
- , Camelia Muresan
- & Michael Murrell
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Article
| Open AccessPatterning and dynamics of membrane adhesion under hydraulic stress
Hydraulic fracturing remodels cell-cell adhesions in physiology and during development. Here, authors combine vesicle experiments and computational modeling to identify the physical principles behind biological fracking.
- Céline Dinet
- , Alejandro Torres-Sánchez
- & Margarita Staykova
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Article
| Open AccessDynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance
The maintenance of cell polarity depends on adhesion complexes that tether to the cytoskeleton. Here the authors show the dynamic nature of E-cadherin–Ankyrin-G complex formation and investigate its functional role in epithelial cell polarity maintenance.
- Chao Kong
- , Xiaozhan Qu
- & Chao Wang
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Article
| Open AccessUbiquitin ligase CHFR mediated degradation of VE-cadherin through ubiquitylation disrupts endothelial adherens junctions
Vascular endothelial cadherin (VE-cadherin), endothelial cell-cell adhesive protein maintains blood vessel barrier integrity and vascular homeostasis. Here, the authors show that infectious bacterial toxin activates ubiquitin ligase CHFR which in turn degrades VEcadherin via ubiquitylation in endothelial cells to cause vascular injury.
- Chinnaswamy Tiruppathi
- , Dong-Mei Wang
- & Asrar B. Malik
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Article
| Open AccessReversible photoregulation of cell-cell adhesions with opto-E-cadherin
Tools for high spatiotemporal control of cell-cell adhesions are lacking. Here, authors propose an optogenetic tool, opto-E-cadherin, that allows reversible control of E-cadherin-mediated cell-cell adhesions with blue light.
- Brice Nzigou Mombo
- , Brent M. Bijonowski
- & Seraphine V. Wegner
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Article
| Open AccessClaudin-23 reshapes epithelial tight junction architecture to regulate barrier function
Claudin family proteins are important for regulating epithelial barrier function. Here the authors show that claudin-23 controls paracellular flux by combining with other claudins to alter tight junction architecture and permeability.
- Arturo Raya-Sandino
- , Kristen M. Lozada-Soto
- & Asma Nusrat
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Article
| Open AccessHexanematic crossover in epithelial monolayers depends on cell adhesion and cell density
Cell monolayers organize themselves with multiscale orientational order. Here, the authors examine how the mechanical and biochemical properties of cells and the substrate affect the crossover between hexatic and nematic orientational order.
- Julia Eckert
- , Benoît Ladoux
- & Thomas Schmidt
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Article
| Open AccessAlk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis
Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. Here, the authors unveil unexpected heterogeneity in the skin VE-cadherin lineage, identifying a dynamic, non-endothelial VE-cadherin+ perineurial cell population.
- Gopal Chovatiya
- , Kefei Nina Li
- & Tudorita Tumbar
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Article
| Open AccessExperimental and theoretical model for the origin of coiling of cellular protrusions around fibers
The leading edges of cellular protrusions coil around extracellular fibers and other fibrous structures such as axons. Combining 3D imaging with theoretical models, the authors show that coiling occurs naturally on curved surfaces due to energy minimization.
- Raj Kumar Sadhu
- , Christian Hernandez-Padilla
- & Nir S. Gov
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Article
| Open AccessIntegrin β3 directly inhibits the Gα13-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis
Zhang et al. show that the adhesion receptor integrin β3 directly inhibits G protein mediated RhoA activation and granule secretion. A peptide mimicking this effect selectively inhibits platelet secretion but not integrin-mediated platelet adhesion.
- Yaping Zhang
- , Xiaojuan Zhao
- & Xiaoping Du
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Article
| Open AccessAllosteric activation of vinculin by talin
Vinculin binding to talin is a key event in focal adhesion dynamics; yet, how vinculin is activated to recruit actin remains unknown. Here, the authors use a multiscale approach to reveal that talin activates vinculin through an intricate allosteric mechanism tightly regulated by force.
- Florian Franz
- , Rafael Tapia-Rojo
- & Frauke Gräter
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Article
| Open AccessCryo-EM structures of full-length integrin αIIbβ3 in native lipids
The structural basis of integrin signaling in health and disease is not fully understood. Here, the authors determine the cryoEM structure of full-length platelet integrin αIIbβ3 in its apo and eptifibatide-bound conformations in a native membrane environment.
- Brian D. Adair
- , Jian-Ping Xiong
- & M. Amin Arnaout
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Article
| Open AccessPlakoglobin is a mechanoresponsive regulator of naive pluripotency
The mechanical microenvironment influences stem cell pluripotency. Here, the authors culture stem cells in microgels with controlled volumetric confinement and identify Plakoglobin as a mechanoresponsive regulator of pluripotency in mouse and human.
- Timo N. Kohler
- , Joachim De Jonghe
- & Florian Hollfelder
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Article
| Open AccessDownregulation of extraembryonic tension controls body axis formation in avian embryos
Extraembryonic tissues provide structural support in addition to signaling inputs. Here they show that extraembryonic structures regulate the mechanical environment of the developing chicken embryo, wherein weakening of the vitelline membrane permits tissue movements that form the body axis.
- Daniele Kunz
- , Anfu Wang
- & Fengzhu Xiong
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Article
| Open AccessNeural crest E-cadherin loss drives cleft lip/palate by epigenetic modulation via pro-inflammatory gene–environment interaction
Cleft lip and palate is a common birth defect thought to involve both genetic and environmental components in its etiology. Here they identify a mechanism involving inflammation and E-cadherin mutations that reduces neural crest migration, leading to craniofacial defects.
- Lucas Alvizi
- , Diogo Nani
- & Roberto Mayor
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Article
| Open AccessChemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes
Dendritic cells can utilize the dynamics of podosomes to probe their microenvironment. Here, the authors propose a chemo-mechanical model for the height oscillations of individual podosomes and the collective wave dynamics in a podosome cluster.
- Ze Gong
- , Koen van den Dries
- & Vivek B. Shenoy
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Article
| Open AccessA Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly
YAP signaling has been established as a mechanotransductive pathway in multiple contexts, but its developmental roles are still being explored. Here they show that YAP signaling sustains intracellular tension to direct cell migration during embryonic axis assembly.
- Ana Sousa-Ortega
- , Javier Vázquez-Marín
- & Juan R. Martínez-Morales
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Article
| Open AccessIn mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells
Adopting a round cell morphology before mitosis is crucial. Here, the authors show that in mitosis integrins binding to ligands do not engage the actomyosin cortex, which curbs cell-extracellular matrix adhesion, though β1 integrins are rewired to synergize with cadherins in mitotic cell-cell adhesion.
- Maximilian Huber
- , Javier Casares-Arias
- & Nico Strohmeyer
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Article
| Open AccessAntigen discrimination by T cells relies on size-constrained microvillar contact
T cells can use TCR on microvilli to interact with peptide-MHC (pMHC) complexes on antigen presenting cells. Here the authors characterise how T cells use microvilli to interrogate reconstituted membranes for pMHC complexes and how this is regulated by a balance between glycoproteins/glycocalyces that reduce detection, and the small adhesion protein CD2, which enhances detection.
- Edward Jenkins
- , Markus Körbel
- & David Klenerman
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Article
| Open AccessMena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.
- Frederic Li Mow Chee
- , Bruno Beernaert
- & Adam Byron
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Article
| Open AccessGrowth anisotropy of the extracellular matrix shapes a developing organ
Tissue morphogenesis is a complex process that involves tissue growth, mechanics, and shape changes. This work demonstrates that differences in growth rate and direction between a tissue layer and its associated extracellular matrix drive 3D shape changes during organ growth.
- Stefan Harmansa
- , Alexander Erlich
- & Thomas Lecuit
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Article
| Open AccessStructure of the planar cell polarity cadherins Fat4 and Dachsous1
Fat and Dachsous are large cadherins that regulate planar polarity as a receptor:ligand pair. Here, authors determine the structure of the Fat:Dachsous complex to uncover the molecular determinants of binding and posttranslational modification.
- Elliot Medina
- , Yathreb Easa
- & Vincent C. Luca
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Article
| Open AccessTRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity
The cortical actin cytoskeleton plays a role in maintaining intestinal epithelial integrity. Here the authors report that TRIM40, an E3 ligase, disrupts cortical actin formation and leads to loss of epithelial barrier integrity, and that genetic loss of TRIM40 is protective against experimental colitis in male mice.
- Sujin Kang
- , Jaekyung Kim
- & Boyoun Park
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Article
| Open AccessVGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid–liquid phase separation
Heart fibrosis involves a feedback loop where stiffening increases fibrosis-related gene expression in myofibroblasts. Here authors reveal the mechanosensitive nuclear translocation of VGLL3, where it phase separates and promotes collagen production, and show that its knock-out is protective after myocardial infarction.
- Yuma Horii
- , Shoichi Matsuda
- & Michio Nakaya
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Article
| Open AccessMultiple pkd and piezo gene family members are required for atrioventricular valve formation
Cardiac valves are essential for heart function, and blood flow stimulation is critical for their formation. Here, researchers have identified a set of mechanosensory genes of the pkd and piezo families as key regulators of valve development.
- Thomas Juan
- , Agatha Ribeiro da Silva
- & Didier Y. R. Stainier
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Article
| Open AccessApremilast prevents blistering in human epidermis and stabilizes keratinocyte adhesion in pemphigus
Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies which destabilize cell adhesion of keratinocytes. The phosphodiesterase 4 inhibitor apremilast prevents skin blistering by stabilizing the keratin filament anchorage of desmosomes.
- Anna M. Sigmund
- , Markus Winkler
- & Jens Waschke
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Article
| Open AccessSingle-molecule characterization of subtype-specific β1 integrin mechanics
Integrins come in subtypes that bind distinct ligands. This work reveals and quantifies subtype-specific mechanical force transmission and assembly of cytoskeleton architectures.
- Myung Hyun Jo
- , Jing Li
- & Taekjip Ha
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Article
| Open AccessFeedback between mechanosensitive signaling and active forces governs endothelial junction integrity
Gap formation in the vasculature underpins immune and tumour cell infiltration. Here the authors propose a chemo-mechanical model to analyse how feedback between mechanosensitive signalling, active cellular forces and adhesion governs the breakdown, recovery, and integrity of endothelial junctions.
- Eoin McEvoy
- , Tal Sneh
- & Vivek B. Shenoy
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Article
| Open AccessProgrammable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation
Human mesenchymal stem cells differentiate in response to mechanical adhesive interactions in their microenvironment. Here, the authors develop a culture platform that can dynamically mimic the cell-cell and cell-extracellular matrix interactions associated with development and mesenchymal differentiation in vivo.
- Zheng Zhang
- , Baoyong Sha
- & Min Lin
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Article
| Open AccessDesign of synthetic collagens that assemble into supramolecular banded fibers as a functional biomaterial testbed
Molecular level control is required to capture the folding and supramolecular assembly of collagen in mimetic materials. Here, the authors report on the creation of a synthetic collagen which assembles into banded fibers, recaptures structural properties of natural collagen and which can act as a testbed for design and experimentation
- Jinyuan Hu
- , Junhui Li
- & Fei Xu
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Article
| Open AccessStructural insights into the contactin 1 – neurofascin 155 adhesion complex
In this work the authors show how a combination of glycosylations, rigid and flexible parts within neurofascin 155 and contactin 1 define a 7.4 nm distance at the myelin-axon interface and allow bridging of three-fold larger distances in the synapse.
- Lucas M. P. Chataigner
- , Christos Gogou
- & Bert J. C. Janssen
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Article
| Open AccessMulticiliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo
Cell integration is a critical process in shaping complex tissues. Ventura and Amiri et al. reveal how multiciliated cells exert forces using filopodia to probe and remodel the neighboring cells, facilitating the formation of a susceptible environment for their integration in vivo.
- Guilherme Ventura
- , Aboutaleb Amiri
- & Jakub Sedzinski
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Article
| Open AccessEpithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation
The epithelial protein Coxsackievirus Adenovirus Receptor (CAR) is a virus receptor but may have other functions. Here the authors show that deletion of CAR in mice leads to reduced house dust mite-induced lung inflammation, reduced neutrophil accumulation and alterations in airway remodelling.
- Elena Ortiz-Zapater
- , Dustin C. Bagley
- & Maddy Parsons
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Article
| Open AccessEya-controlled affinity between cell lineages drives tissue self-organization during Drosophila oogenesis
Oogenesis depends on close interaction between germ cells and the surrounding somatic niche. Here the authors demonstrate that Eya controls bilateral affinity at the germline-soma interface to generate self-organizing inter-lineage units that ensure oocyte maturation.
- Vanessa Weichselberger
- , Patrick Dondl
- & Anne-Kathrin Classen
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Article
| Open AccessThe Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.
- Hongyu Shen
- , Xun Huang
- & Yifu Qiu
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Article
| Open AccessOptineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division
Uropathogenic strains of Escherichia coli (UPEC) are a leading cause of urinary tract infections (UTIs) and invasion involves Rho GTPase members, notably Rac1, to drive actin cytoskeleton rearrangement leading to engulfment. Here, Petracchini et al. provide evidence of an ECM stiffnessmodulated role of Optineurin (OPTN), which regulates HACE1-dependant Rac1 activity and thus controls integrinmediated mechanotransduction and bacterial invasion.
- Serena Petracchini
- , Daniel Hamaoui
- & Amel Mettouchi
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Article
| Open AccessAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
The functional role of airway basal cells has not been comprehensively studied in idiopathic pulmonary fibrosis (IPF). Here, the authors show that airway basal cells of IPF patients display a distinct phenotype, are profibrotic if transplanted to mice and that fibrosis can be ameliorated by Src iinhibitors.
- Benedikt Jaeger
- , Jonas Christian Schupp
- & Antje Prasse