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Microfluidic cell encapsulation has provided a platform for studying the behavior of individual cells and has become a turning point in single-cell analysis during the last decade. The engineered microenvironment, along with protecting the immune response, has led to increasingly presenting the results of practical and pre-clinical studies with the goals of disease treatment, tissue engineering, intelligent control of stem cell differentiation, and regenerative medicine. However, the significance of cell-substrate interaction versus cell-cell communications in the microgel is still unclear. In this study, monodisperse alginate microgels were generated using a flow-focusing microfluidic device to determine how the cell microenvironment can control human bone marrow-derived mesenchymal stem cells (hBMSCs) viability, proliferation, and biomechanical features in single-cell droplets versus multi-cell droplets. Collected results show insufficient cell proliferation (234 % and 329 %) in both single- and multi-cell alginate microgels. Alginate hydrogels supplemented with poly- l -lysine (PLL) showed a better proliferation rate (514 % and 780 %) in a comparison of free alginate hydrogels. Cell stiffness data illustrate that hBMSCs cultured in alginate hydrogels have higher membrane flexibility and migration potency (Young's modulus equal to 1.06 kPa), whereas PLL introduces more binding sites for cell attachment and causes lower flexibility and migration potency (Young's modulus equal to 1.83 kPa). Considering that cell adhesion is the most important parameter in tissue engineering, in which cells do not run away from a 3D substrate, PLL enhances cell stiffness and guarantees cell attachments. In conclusion, cell attachment to PLL-mediated alginate hydrogels is crucial for cell viability and proliferation. It suggests that cell-cell signaling is good enough for stem cell viability, but cell-PLL attachment alongside cell-cell signaling is crucial for stem cell proliferation and self-renewal. • Microfluidic single cell encapsulation is used as a platform for studying cell-substrate and cell-cell interaction. • The cell microenvironment promotes stem cell viability and proliferation. • Cell-substrate interaction affects stem cell mechanical behavior, which reduces cell migration tendency. • Cell-substrate interaction is essential for the initiation of cell-cell crosstalk and leads to proliferation signaling. [ABSTRACT FROM AUTHOR]

Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of ‘reverse evolution’ of the self-same processes. [ABSTRACT FROM AUTHOR]

The Gram-positive, anaerobic, spore-forming, rod-shaped Clostridium perfringens is widely distributed in nature, especially in soil and the gastrointestinal tract of humans and animals. C. perfringens causes clostridial myonecrosis (or gas gangrene), enteritis and enterotoxemia in humans and livestock by producing numerous extracellular toxins and enzymes. The toxin gene expression is regulated by a two-component regulatory system and regulatory RNA VirR/VirS-VR-RNA cascade. The VirR/VirS system was originally found in a type A strain, but a recent report showed that it is also important for the toxin gene regulation in other types of strains. Two types of cell–cell signaling, i.e., agr -system and AI-2 signaling, are also important for the regulation of toxin genes. Several regulatory systems independent from the VirR/VirS system, including virX , the orphan histidine kinase ReeS and orphan response regulator RevR, are also involved in the regulation of toxin genes. In addition, the expression of toxin genes is upregulated after contact with Caco-2 cells. C. perfringens has a complex regulatory network for toxin gene expression and thus the coordination of toxin gene expression is important for the process of infection. [ABSTRACT FROM AUTHOR]

Polybacterial diseases involve multiple organisms that act collectively to facilitate disease progression. Although this phenomenon was highlighted early in the 20th century, recent technological advances in diagnostics have led to the appreciation that many infections are far more complex than originally believed. Furthermore, it is apparent that although most treatments focus on the dominant bacterial species in an infection, other microbes, including commensals, can have a profound impact on both the response to therapy and virulence. Very little is known about the molecular mechanisms that underpin interactions between bacteria during such infections. Here, we discuss recent studies identifying and characterizing mechanisms of bacterial interaction and the biological processes they govern during certain diseases. We also highlight how possible strategies for targeting these interbacterial interactions may afford a route towards development of new therapies, with consequences for disease control. [ABSTRACT FROM AUTHOR]

Abstract: Myxobacteria exhibit complex social traits during which large populations of cells coordinate their behaviors. An iconic example is their response to starvation: thousands of cells move by gliding motility to build a fruiting body in which vegetative cells differentiate into spores. Here we review mechanisms that the model species Myxococcus xanthus uses for cell–cell interactions, with a focus on developmental signaling and social gliding motility. We also discuss a newly discovered cell–cell interaction whereby myxobacteria exchange their outer membrane (OM) proteins and lipids. The mechanism of OM transfer requires physical contact between aligned cells on a hard surface and is apparently mediated by OM fusion. The TraA and TraB proteins are required in both donor and recipient cells for transfer, suggesting bidirectional exchange, and TraA is thought to serve as a cell surface adhesin. OM exchange results in phenotypic changes that can alter gliding motility and development and is proposed to represent a novel microbial interacting platform to coordinate multicellular activities. [Copyright &y& Elsevier]

Abstract: Citrus limonoids were reported to inhibit autoinducer-mediated bacterial cell–cell signaling, Escherichia coli O157:H7 biofilms and the Type III secretion system. The goal of the present study was to understand the effect of specific modifications in limonin molecule on cell–cell signaling inhibitory activity. The limonin was modified into de-furan limonin, limonin 7-oxime, limonin 7-methoxime. The modified limonoids were examined for their cell–cell signaling and biofilm inhibitory properties. The results of the study suggest that the furan ring and C-7 substitutions were important structural features in the limonin molecule to inhibit cell–cell signaling and biofilm formation in Vibrio harveyi. The C-7 modifications of limonin showed increased potency to inhibit the E. coli biofilm. Furthermore, the data indicates that limonin 7-methoxime reduced the attachment of E. coli to plastic surface by interacting with type 1 pili and Ag43. In addition, limonin 7-methoxime seems to reduce the adhesion of E. coli to spinach leaves and colon epithelial cells. [Copyright &y& Elsevier]

Abstract: Rb1 is a tumor suppressor gene that regulates cell cycle progression through interactions with E2F transcription factors. In recent years, new roles for Rb1 in regulating cellular differentiation have also emerged. For example, it has been shown that Rb1 regulates osteoblast differentiation in a cell cycle independent manner, by binding to the transcription factor Runx2, and facilitating the up-regulation of late bone differentiation markers. Based on the facts that Runx2 also functions in tooth development, and that little is known about potential roles for Rb1 in mammalian tooth development, here we evaluated the expression of Rb1 mRNA in developmentally staged mouse teeth. Our data show that Rb1 mRNA is expressed in both dental epithelial and dental mesenchymal progenitor cells. In addition, Rb1 mRNA appears upregulated in differentiating ameloblasts and odontoblasts, suggesting roles for Rb1 in tooth differentiation. [Copyright &y& Elsevier]

The solution to the problem of evolution has proven refractory to experimentation-how fish have evolved into Man phylogenetically, for example-because evolution is thought to be due to random mutations, obviating the opportunity to test such a mechanism, leaving only correlations and associations, which do not show causation. Ideally, there would be some comparable process that could be exploited in order to deconvolute evolution, but none had been forthcoming up until now, having been introduced to Knot Theory, a subheading of Topology. Topology concerns itself with how geometric objects maintain themselves under continuous deformations. Knot Theory is the study of mathematical knots, inspired by the knots that occur in everyday life. It occurred to us that since knots tie things together, they are similar in kind to the cell-cell signaling mechanisms that tie physiologic traits together during development, culminating in physiology, tied together by homeostasis. [ABSTRACT FROM AUTHOR]

Abstract: Cell-to-cell communications in bacteria mediated by small diffusible molecules termed as autoinducers (AI) are known to influence gene expression and pathogenicity. Oligopeptides and N-acylhomoserine lactones (AHL) are major AI molecules involved in intra-specific communication in Gram-positive and Gram-negative bacteria respectively, whereas boronated-diester molecules (AI-2) are involved in inter-specific communication among both Gram-positive and Gram-negative bacteria. Naturally occurring furocoumarins from grapefruit showed >95% inhibition of AI-1 and AI-2 activities based on the Vibrio harveyi based autoinducer bioassay. Grapefruit juice and furocoumarins also inhibited biofilm formation by Escherichia coli O157:H7, Salmonella typhimurium and Pseudomonas aeruginosa. These results suggest that grape fruit juice and furocoumarins could serve as a source to develop bacterial intervention strategies targeting microbial cell signaling processes. [Copyright &y& Elsevier]

Abstract: The synthesis of virulence factors in the plant pathogen Xanthomonas campestris pathovar campestris is regulated by cell–cell signaling mediated by a diffusible signal factor (DSF), and by the RpfC/RpfG two-component regulatory system. Recent findings have indicated that the perception of the DSF signal requires the RpfC sensor and is linked to the degradation of the intracellular second messenger cyclic di-GMP by the HD-GYP domain regulator RpfG. [Copyright &y& Elsevier]

Mitochondrial antiviral signaling (MAVS) protein mediates innate antiviral responses, including responses to certain coronaviruses such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have previously shown that ultraviolet-A (UVA) therapy can prevent virus-induced cell death in human ciliated tracheal epithelial cells (HTEpC) infected with coronavirus-229E (CoV-229E), and results in increased intracellular levels of MAVS. In this study, we explored the mechanisms by which UVA light can activate MAVS, and whether local UVA light application can activate MAVS at locations distant from the light source (e.g. via cell-to-cell communication). MAVS levels were compared in HTEpC exposed to 2 mW/cm2 narrow band (NB)-UVA for 20 min and in unexposed controls at 30–40% and at 100% confluency, and in unexposed HTEpC treated with supernatants or lysates from UVA-exposed cells or from unexposed controls. MAVS was also assessed in different sections of confluent monolayer plates where only one section was exposed to NB-UVA. Our results showed that UVA increases the expression of MAVS protein. Further, cells in a confluent monolayer exposed to UVA conferred an elevation in MAVS in cells adjacent to the exposed section, and also in cells in the most distant sections which were not exposed to UVA. In this study, human ciliated tracheal epithelial cells exposed to UVA demonstrate increased MAVS protein, and also appear to transmit this influence to confluent cells not exposed to UVA, likely via cell-cell signaling. • Ultraviolet-A (UVA) light induces mitochondrial antiviral signaling (MAVS) protein. • Localized UVA therapy induces MAVS in distant non-exposed confluent monolayer cells. • UVA induction of MAVS does not involve secreted extracellular mediators. • UVA induction of MAVS in distant cells may involve cell-to-cell signaling. [ABSTRACT FROM AUTHOR]

Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Here we report a protocol differentiating human pluripotent stem cells into endometrial stromal fibroblasts (PSC-ESFs) that are highly pure and able to decidualize. Coculture of PSC-ESFs with placenta-derived endometrial epithelial cells generated organoids used to examine stromal-epithelial interactions. Cocultures exhibited specific endometrial markers in the appropriate compartments, organization with cell polarity, and hormone responsiveness of both cell types. Furthermore, cocultures recapitulate a central feature of the human decidua by cyclically responding to hormone withdrawal followed by hormone retreatment. This advance enables mechanistic studies of the cyclic responses that characterize the human endometrium. [Display omitted] • Endometrial stromal fibroblasts can be differentiated from human ESCs and iPSCs (PSCs) • PSC-ESFs self-assemble with endometrial epithelial organoids • Cocultured PSC-ESFs and EEOs cyclically respond to hormone treatment and withdrawal • PSC-ESFs respond to epithelial cell signaling while in coculture Cheung et al. report a 3-dimensional in vitro model of the human decidua composed of hormone-responsive endometrial stromal fibroblasts differentiated through developmental intermediates from pluripotent stem cells (PSC-ESFs) and epithelial cells derived from postpartum decidua. PSC-ESFs associate with and respond to epithelial cells and cyclic hormone treatment and withdrawal. [ABSTRACT FROM AUTHOR]