scholarly journals Lymph node tissue homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics

Author(s):  
Harry Horsnell ◽  
Robert Tetley ◽  
Henry De Belly ◽  
Spyridon Makris ◽  
Lindsey Millward ◽  
...  

Abstract Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular physical properties, collectively determining tissue mechanics of lymph nodes, an immunologically-relevant, adult mammalian tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive tissue expansion upon immune challenge. We find that following immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that CLEC-2/podoplanin signalling regulates the cell surface mechanics of fibroblasts, permitting cell elongation and interdigitation through expedited access to plasma membrane reservoirs. Increased tissue tension through the stromal meshwork gates the initiation of fibroblast proliferation, restoring homeostatic cellular ratios and tissue structure through expansion.

2018 ◽  
Author(s):  
Robert J. Tetley ◽  
Michael F. Staddon ◽  
Shiladitya Banerjee ◽  
Yanlan Mao

SummaryEpithelial tissues are inevitably damaged from time to time and must therefore have robust repair mechanisms. The behaviour of tissues depends on their mechanical properties and those of the surrounding environment1. However, it remains poorly understood how tissue mechanics regulates wound healing, particularly in in vivo animal tissues. Here we show that by tuning epithelial cell junctional tension, we can alter the rate of wound healing. We observe cells moving past each other at the wound edge by intercalating, like molecules in a fluid, resulting in seamless wound closure. Using a computational model, we counterintuitively predict that an increase in tissue fluidity, via a reduction in junctional tension, can accelerate the rate of wound healing. This is contrary to previous evidence that actomyosin tensile structures are important for wound closure2–6. When we experimentally reduce tissue tension, cells intercalate faster and wounds close in less time. The role we describe for tissue fluidity in wound healing, in addition to its known roles in developing7,8 and mature tissues9, reinforces the importance of the fluid state of a tissue.


2019 ◽  
Author(s):  
Hye Young Kim ◽  
Timothy R. Jackson ◽  
Carsten Stuckenholz ◽  
Lance A. Davidson

AbstractInjury, surgery, and disease often disrupt tissues and it is the process of regeneration that aids the restoration of architecture and function. Regeneration can occur through multiple strategies including induction of stem cell expansion, transdifferentiation, or proliferation of differentiated cells. We have uncovered a case of regeneration that restores a mucociliated epithelium from mesenchymal cells. Following disruption of embryonic tissue architecture and assembly of a compact mesenchymal aggregate, regeneration first involves restoration of an epithelium, transitioning from mesenchymal cells at the surface of the aggregate. Cells establish apico-basal polarity within 5 hours and a mucociliated epithelium within 24. Regeneration coincides with nuclear translocation of the putative mechanotransducer YAP1 and a sharp increase in aggregate stiffness, and regeneration can be controlled by altering stiffness. We propose that regeneration of a mucociliated epithelium occurs in response to biophysical cues sensed by newly exposed cells on the surface of a disrupted mesenchymal tissue.


2017 ◽  
Author(s):  
Emanuel Rognoni ◽  
Angela Oliveira Pisco ◽  
Toru Hiratsuka ◽  
Kalle Sipilä ◽  
Julio M. Belmonte ◽  
...  

SummaryMurine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.Standfirst textWe show that fibroblast behaviour switching between two distinct states – proliferating and depositing ECM - is necessary and sufficient to define dermal architecture. Understanding this interdependence is critical for identifying new therapeutic strategies to enhance skin regeneration.HighlightsTissue-scale coordination in murine dermis is driven by the interdependence of cell proliferation and ECM depositionThe tissue architecture is set by a negative feedback loop between ECM deposition/remodelling and proliferationFibroblast lineages lose segregation with ageFibroblast migration is the critical discriminator between dermal development and wound healing


2019 ◽  
Author(s):  
Natalie J. Kirkland ◽  
Alice C. Yuen ◽  
Melda Tozluoglu ◽  
Nancy Hui ◽  
Ewa K. Paluch ◽  
...  

SummaryCell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical to preserve tissue integrity during cell division. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Yet, inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We then use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We also find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Strikingly, perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis. We speculate that mechanical regulation of apical mitotic positioning could be a global mechanism for tissue growth control.


2017 ◽  
Author(s):  
Ricardo J Miragaia ◽  
Tomás Gomes ◽  
Agnieszka Chomka ◽  
Laura Jardine ◽  
Angela Riedel ◽  
...  

SummaryNon-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype of which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, the respective draining lymph nodes and spleen. From this data, we modelled a continuous lymphoid-to-NLT trajectory for Treg, and reconstructed the mechanisms of cell migration and NLT adaption. This revealed a shared transcriptional programme of NLT priming in both skin and colon-associated lymph nodes, followed by tissue-specific adaptation. Predicted migration kinetics were validated using a melanoma-induction model, emphasizing the relevance of key regulators and receptors, including Batf, Rora, Ccr8, Samsn1. Finally, we profiled human blood and NLT Treg and Tmem cells, identifying cross-mammalian conserved tissue signatures. In summary, we have identified molecular signals mediating NLT Treg recruitment and tissue adaptation through the combined use of computational prediction and in vivo validation.


1949 ◽  
Vol 181 (1) ◽  
pp. 237-245 ◽  
Author(s):  
Adolph. Abrams ◽  
Philip P. Cohen ◽  
Ovid O. Meyer

1976 ◽  
Vol 32 ◽  
pp. 365-377 ◽  
Author(s):  
B. Hauck
Keyword(s):  

The Ap stars are numerous - the photometric systems tool It would be very tedious to review in detail all that which is in the literature concerning the photometry of the Ap stars. In my opinion it is necessary to examine the problem of the photometric properties of the Ap stars by considering first of all the possibility of deriving some physical properties for the Ap stars, or of detecting new ones. My talk today is prepared in this spirit. The classification by means of photoelectric photometric systems is at the present time very well established for many systems, such as UBV, uvbyβ, Vilnius, Geneva and DDO systems. Details and methods of classification can be found in Golay (1974) or in the proceedings of the Albany Colloquium edited by Philip and Hayes (1975).


Author(s):  
Frederick A. Murphy ◽  
Alyne K. Harrison ◽  
Sylvia G. Whitfield

The bullet-shaped viruses are currently classified together on the basis of similarities in virion morphology and physical properties. Biologically and ecologically the member viruses are extremely diverse. In searching for further bases for making comparisons of these agents, the nature of host cell infection, both in vivo and in cultured cells, has been explored by thin-section electron microscopy.


Author(s):  
K.P.D. Lagerlof

Although most materials contain more than one phase, and thus are multiphase materials, the definition of composite materials is commonly used to describe those materials containing more than one phase deliberately added to obtain certain desired physical properties. Composite materials are often classified according to their application, i.e. structural composites and electronic composites, but may also be classified according to the type of compounds making up the composite, i.e. metal/ceramic, ceramic/ceramie and metal/semiconductor composites. For structural composites it is also common to refer to the type of structural reinforcement; whisker-reinforced, fiber-reinforced, or particulate reinforced composites [1-4].For all types of composite materials, it is of fundamental importance to understand the relationship between the microstructure and the observed physical properties, and it is therefore vital to properly characterize the microstructure. The interfaces separating the different phases comprising the composite are of particular interest to understand. In structural composites the interface is often the weakest part, where fracture will nucleate, and in electronic composites structural defects at or near the interface will affect the critical electronic properties.


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