Extracellular Matrix News Volume 11.01 | Jan 16 2020

TOP STORY

Syndecan-4 Tunes Cell Mechanics by Activating the Kindlin-Integrin-RhoA Pathway

Researchers revealed a mechanism whereby syndecan-4 tuned cell mechanics in response to localized tension via a coordinated mechanochemical signaling response that involved activation of two other receptors: epidermal growth factor receptor and β1 integrin. Tension on syndecan-4 induced cell-wide activation of the kindlin-2/β1 integrin/RhoA axis in a PI3K-dependent manner. [Nat Mater] Abstract

(Ranked by impact factor of the journal)

The LC3-Conjugation Machinery Specifies the Loading of RNA-Binding Proteins into Extracellular Vesicles

The secretome consisted of a highly interconnected network enriched in RNA-binding proteins and extracellular vesicles (EV) cargoes. Proteomic and RNA profiling of EVs identified diverse RNA-binding proteins and small non-coding RNAs requiring the LC3-conjugation machinery for packaging and secretion. [Nat Cell Biol] Abstract

Tissue-Resident PDGFRα⁺ Progenitor Cells Contribute to Fibrosis versus Healing in a Context- and Spatiotemporally Dependent Manner

The authors showed that PDGFRα⁺ cells were essential for tissue revascularization and restructuring through injury-stimulated remodeling of stromal and vascular components, context-dependent clonal expansion, and ultimate removal of pro-fibrotic PDGFRα⁺-derived cells. Tissue ischemia modulated the PDGFRα⁺ phenotype toward cells capable of remodeling the ECM and inducing cell-cell and cell-matrix adhesion, likely favoring tissue repair. [Cell Rep] Full Article | Graphical Abstract

Mouse Ovarian Cancer Models Recapitulate the Human Tumor Microenvironment and Patient Response to Treatment

Scientists characterized the tumor microenvironment (TME) of six orthotopic, transplantable syngeneic murine high-grade serous ovarian cancer lines established from genetic models and comparef these to patient biopsies. They identified significant correlations between the transcriptome, host cell infiltrates, matrisome, vasculature, and tissue modulus of mouse and human TMEs, with several stromal and malignant targets in common. [Cell Rep] Full Article | Graphical Abstract

Extracellular Electron Uptake in Methanosarcinales Is Independent of Multiheme C-Type Cytochromes

Researchers tested eleven new co-culture combinations between methanogens and electrogens. Previously, only the most electrogenic Geobacter paired by DIET with Methanosarcinales methanogens, namely G. metallireducens and G. hydrogenophilus. They provided additional support, and showed that five additional Methanosarcinales paired with G. metallireducens, while a strict hydrogenotroph could not. [Sci Rep] Full Article

Calcite Incorporated in Silica/Collagen Xerogels Mediates Calcium Release and Enhances Osteoblast Proliferation and Differentiation

On the first level, low fibrillar collagen served as template for silica nanoparticle agglomerates. On second level, this silica-enriched matrix phase was fiber-reinforced by collagen fibrils. [Sci Rep] Full Article

Reduction of the Therapeutic Dose of Silencing RNA by Packaging It in Extracellular Vesicles via a Pre-MicroRNA Backbone

Investigators showed that the integration of siRNA sequences into a Dicer-independent RNA stem-loop based on pre-miR-451 microRNA-which was highly enriched in small extracellular vesicles secreted by many cell types-reduced the expression of the genes targeted by the siRNA in the liver, intestine and kidney glomeruli of mice at siRNA doses that were at least tenfold lower than the siRNA doses typically delivered via lipid nanoparticles. [Nat Biomed Eng] Abstract

Surrogate R-Spondins for Tissue-Specific Potentiation of Wnt Signaling

The authors describe the engineering of ‘surrogate RSPOs’ that function independently of leucine-rich repeat-containing G-protein coupled receptors to potentiate Wnt signaling on cell types expressing a target surface marker. These bispecific proteins were generated by fusing an RNF43- or ZNRF3-specific single chain antibody variable fragment to the immune cytokine IL-2. [PLoS One] Full Article

The Matrix Vesicle Cargo miR-125b Accumulates in the Bone Matrix, Inhibiting Bone Resorption in Mice

Scientists describe an unexpected role for matrix vesicles (MVs), which budded from bone-forming osteoblasts and had a well-established role in initiation of bone mineralization, in osteoclastogenesis. They showed that the MV cargo miR-125b accumulated in the bone matrix, with increased accumulation in transgenic mice overexpressing miR-125b in osteoblasts. [Commun Biol] Full Article

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Bioengineered 3D Models to Recapitulate Tissue Fibrosis

The authors focus on the recent multidisciplinary developments made towards advanced 3D biomimetic fibrotic tissue models that combine highly precision manufacturing techniques with high cellular functionality and biophysical properties. [Trends Biotechnol] Abstract

Peri/Epicellular Thiol Oxidoreductases as Mediators of Extracellular Redox Signaling

Supracellular redox networks regulating cell-ECM and organ system architecture merge with structural and functional properties of disulfide bonds. Investigators address emerging evidence that exported thiol oxidoreductases(TOR) such as thioredoxin, protein disulfide isomerases, QSOX1 and peroxiredoxins, composing a peri/epicellular (pec)TOR pool, mediates relevant signaling. [Antioxid Redox Signal] Abstract

Therapeutic Vascularization in Regenerative Medicine: Concise Review

Scientists briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. [Stem Cells Transl Med] Full Article

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

Scholar Rock Receives $25M for Continued Research in Potential Therapies for Fibrotic Diseases

Biopharmaceutical company Scholar Rock received $25 million from Gilead Sciences to continue the development of potential therapies to treat the progression of fibrotic diseases, including pulmonary fibrosis. This funding is a milestone payment, based on Scholar Rock’s preclinical studies in animals showing the effectiveness of therapeutic compounds that can block the activation of a factor called transforming growth factor beta. [Scholar Rock (Pulmonary Fibrosis News)] Press Release

Nine Researchers Receive EMBO Installation Grants to Establish Independent Laboratories

EMBO is pleased to announce that nine life scientists have been selected to receive Installation Grants, which will support them in establishing independent laboratories in the Czech Republic, Poland, Portugal and Turkey. [EMBO (EurekAlert!)] Press Release

Florida Cracks Down on Foreign Government Involvement in Research

Florida is launching a statewide investigation into US research exploitation after four University of Florida faculty members and six employees of Moffitt Cancer Center in Tampa failed to disclose ties to foreign programs, reports the Tampa Bay Times. [The Scientist] Editorial

NIH Extends Reporting Mandate to More Clinical Trials, but Obscures Their Policing

Many companies and medical research institutions fail to meet a long-standing legal mandate to disclose clinical trial results in a federal database. For certain trials, however, compliance is impossible to verify. [ScienceInsider] Editorial

NEW Undoing Aging 2020
March 21-23, 2020
Berlin, Germany

Visit our events page to see a complete list of events in the community.

NEW Research Associate – Bioengineering (STEMCELL Technologies Inc.)

NEW Postdoctoral Researcher – Computational Biology (Medical University of Gdańsk)

Research Associate – Oncology (Zymeworks Inc.)

Research Fellow – Cell Signaling (University of Sussex)

Research Scientist – Tumor Microenvironment (Systimmune Inc.)

Postdoctoral Researcher – Tumor Microenvironment (Personalis, Inc.)

Postdoctoral Research Fellow – Tumor Microenvironment (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Inter- and Extracellular Protein Interactions (University of Southern California)

Scientist – Regenerative Medicine (Xtant Medical, Inc.)

Master Thesis – Hydrogels and Microfluid Environments (Karlsruhe Institute of Technology)

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