fibroblastic cell
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2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Joern Pezoldt ◽  
Carolin Wiechers ◽  
Florian Erhard ◽  
Ulfert Rand ◽  
Tanja Bulat ◽  
...  

AbstractOur understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches. We further identify striking differences in innate immune signatures of distinct stromal compartments in vivo. Compared to other fibroblasts and to endothelial cells, Ly6C+ fibroblasts of the red pulp were selectively endowed with enhanced interferon-stimulated gene expression in homeostasis, upon systemic interferon stimulation and during virus infection in vivo. Collectively, we provide an updated map of fibroblastic cell diversity in the spleen that suggests a specialized innate immune function for splenic red pulp fibroblasts.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1193
Author(s):  
Paolo Giannoni ◽  
Marco Grosso ◽  
Giuseppina Fugazza ◽  
Mario Nizzari ◽  
Maria Cristina Capra ◽  
...  

Hypersensitivity pneumonitis (HP) is a diffuse interstitial lung disease (ILD) caused by the inhalation of a variety of antigens in susceptible individuals. Patients with fibrotic HP (fHP) may show histopathological and radiological manifestations similar to patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia-like pattern of fibrosis) that are associated with a worse prognosis. We describe here the establishment and characterization of a fibroblastic cell line derived from the broncho-alveolar lavage (BAL) of a patient with fHP, a 53 year old man who presented at our Pneumology Unit with cough and dyspnea. The fHP diagnosis was based on international criteria and multidisciplinary discussion. Primary fibroblasts were expanded in vitro until passage 36. These fibroblasts displayed morpho/phenotypical features of myofibroblasts, showing high positivity for α-smooth muscle actin, type I collagen, and fibronectin as determined by quantitative RT-PCR and cyto-fluorographic analysis. Cytogenetic analyses further evidenced trisomy of chromosome 10, which interestingly harbors the FGF2R gene. To our knowledge, this is the first fibroblastic cell line derived from an fHP patient and might, therefore, represent a suitable tool to model the disease in vitro. We preliminarily assessed here the activity of pirfenidone, further demonstrating a consistent inhibition of cells growth by this antifibrotic drug.


Author(s):  
Lavanya Kubendiran ◽  
Sowmiya Theerthagiri ◽  
Naif Abdullah Al-Dhabi ◽  
Senthilkumar Palaninaicker ◽  
Shivakumar Muthugoundar Subramanian ◽  
...  

Author(s):  
Kathryn M. Kim ◽  
Mentor Thaqi ◽  
Daniel A. Peterson ◽  
Robert A. Marr

Direct cellular reprogramming exhibits distinct advantages over reprogramming from an induced pluripotent stem cell intermediate. These include a reduced risk of tumorigenesis and the likely preservation of epigenetic data. In vitro direct reprogramming approaches primarily aim to model the pathophysiological development of neurological disease and identify therapeutic targets, while in vivo direct reprogramming aims to develop treatments for various neurological disorders, including cerebral injury and cancer. In both approaches, there is progress toward developing increased control of subtype-specific production of induced neurons. A majority of research primarily utilizes fibroblasts as the donor cells. However, there are a variety of other somatic cell types that have demonstrated the potential for reprogramming into induced neurons. This review highlights studies that utilize non-fibroblastic cell sources for reprogramming, such as astrocytes, olfactory ensheathing cells, peripheral blood cells, Müller glia, and more. We will examine benefits and obstructions for translation into therapeutics or disease modeling, as well as efficiency of the conversion. A summary of donor cells, induced neuron types, and methods of induction is also provided.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Abinash Padhi ◽  
Karanpreet Singh ◽  
Janusz Franco-Barraza ◽  
Daniel J. Marston ◽  
Edna Cukierman ◽  
...  

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Abinash Padhi ◽  
Karanpreet Singh ◽  
Janusz Franco-Barraza ◽  
Daniel J. Marston ◽  
Edna Cukierman ◽  
...  

AbstractAligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify “3D perpendicular lateral protrusions” (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion.


2020 ◽  
Author(s):  
Juan Li ◽  
Ping Li ◽  
Guojun Zhang ◽  
Pan Qin ◽  
Da Zhang ◽  
...  

Abstract The excessive activation and proliferation of lung fibroblasts are responsible for the abundant deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF), while its specific mechanism is still unknown. This study focuses on the role of circRNA (circ) TADA2A in functional abnormalities of lung fibroblasts and aims to elaborate its regulatory mechanism. In the present study, circTADA2A was down-regulated in both IPF primary human lung fibroblasts and human IPF fibroblastic cell lines. Functionally, the overexpression of circTADA2A repressed the activation and proliferation of normal human fibroblastic cell line induced by several fibrogenic growth factors. Using fluorescence in situ hybridization (FISH), luciferase reporter assays, and RNA pull-down, circTADA2A was confirmed to function as sponges of miR-526b and miR-203, thus releasing the expression of Caveolin (Cav)-1 and Cav-2. The overexpression of circTADA2A suppressed lung fibroblasts activation via Cav-1 and reduced lung fibroblasts proliferation via Cav-2. In vivo experiments also confirmed that the overexpression of circTADA2A decreased fibrogenic responses induced by bleomycin in lung fibrosis mice. Collectively, circTADA2A repressed lung fibroblasts activation via miR-526b/Cav-1 and reduced lung fibroblasts proliferation via miR-203/Cav-2, thus inhibiting the excessive deposition of ECM and relieving IPF.


Author(s):  
Janusz Franco-Barraza ◽  
Kristopher S. Raghavan ◽  
Tiffany Luong ◽  
Edna Cukierman

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