Long-term imaging and spatio-temporal control of living cells using targeted light based on closed-loop feedback.

Unlabelled: The ability to optically interact with cells on both an individual and collective level has applications from wound healing to cancer treatment. Building systems that can facilitate both localised light illumination and visualisation of cells can, however, be challenging and costly. This work takes the Dynamic Optical MicroEnvironment (DOME), an existing platform for the closed-loop optical control of microscale agents, and adapts the design to support live-cell imaging.

The PECAn image and statistical analysis pipeline identifies Minute cell competition genes and features.

Investigating organ biology often requires methodologies to induce genetically distinct clones within a living tissue. However, the 3D nature of clones makes sample image analysis challenging and slow, limiting the amount of information that can be extracted manually. Here we develop PECAn, a pipeline for image processing and statistical data analysis of complex multi-genotype 3D images.

Meaningful steps toward equity, diversity, and inclusion: A call to action.

EDI allies congregated to highlight initiatives intended to address barriers to research opportunities and support that could promote recruitment and retention of diverse talent, encourage collaborative research, improve community engagement, and cultivate public trust in research.

ISSCR Education Committee syllabus and learning guide for enhancing stem cell literacy.

The rapidly evolving stem cell field puts much stress on developing educational resources. The ISSCR Education Committee has created a flexible stem cell syllabus rooted in core concepts to facilitate stem cell literacy. The free syllabus will be updated regularly to maintain accuracy and relevance.

The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.

Gustatory Receptor 64 (Gr64) genes are a cluster of 6 neuronally expressed receptors involved in sweet taste sensation in Drosophila melanogaster. Gr64s modulate calcium signalling and excitatory responses to several different sugars. Here, we discover an unexpected nonneuronal function of Gr64 receptors and show that they promote proteostasis in epithelial cells affected by proteotoxic stress.

p53 directs leader cell behavior, migration, and clearance during epithelial repair.

Epithelial cells migrate across wounds to repair injured tissue. Leader cells at the front of migrating sheets often drive this process. However, it is unclear how leaders emerge from an apparently homogeneous epithelial cell population.

Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status.

Cell competition induces the elimination of less-fit "loser" cells by fitter "winner" cells. In Drosophila, cells heterozygous mutant in ribosome genes, Rp/+, known as Minutes, are outcompeted by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status.

Mechanical cell competition in human pluripotent stem cell cultures.

Human induced pluripotent stem cells (hIPSCs) are an important tool, but challenges remain in optimizing their use. hIPSC cultures frequently become contaminated and overrun with cells containing genetic aberrations. In this issue of Developmental Cell, Price et al.

Proteotoxic stress is a driver of the loser status and cell competition.

Cell competition allows winner cells to eliminate less fit loser cells in tissues. In Minute cell competition, cells with a heterozygous mutation in ribosome genes, such as RpS3 cells, are eliminated by wild-type cells. How cells are primed as losers is partially understood and it has been proposed that reduced translation underpins the loser status of ribosome mutant, or Minute, cells.

Publisher Correction: Outcompeting cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Outcompeting cancer.

The tumour microenvironment plays a critical role in determining tumour fate. Within that environment, and indeed throughout epithelial tissues, cells experience competition with their neighbours, with those less fit being eliminated by fitter adjacent cells. Herein we discuss evidence suggesting that mutations in cancer cells may be selected for their ability to exploit cell competition to kill neighbouring host cells, thereby facilitating tumour expansion.

Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status.

Cell competition is a form of cell interaction that causes the elimination of less fit cells, or losers, by wild-type (WT) cells, influencing overall tissue health. Several mutations can cause cells to become losers; however, it is not known how. Here we show that Drosophila wing disc cells carrying functionally unrelated loser mutations (Minute and mahjong) display the common activation of multiple stress signalling pathways before cell competition and find that these pathways collectively account for the loser status.

FGFR2 is required for airway basal cell self-renewal and terminal differentiation.

Airway stem cells slowly self-renew and produce differentiated progeny to maintain homeostasis throughout the lifespan of an individual. Mutations in the molecular regulators of these processes may drive cancer or degenerative disease, but are also potential therapeutic targets. Conditionally deleting one copy of FGF receptor 2 (FGFR2) in adult mouse airway basal cells results in self-renewal and differentiation phenotypes.

Epithelial Homeostasis: A Piezo of the Puzzle.

A recent study shows that, upon stretching or wounding, epithelia display a fast proliferative response that allows for re-establishment of optimal cell density or sealing of the wound. This increased proliferation is induced by the stretch-activated channel Piezo1 and involves calcium-triggered ERK signalling.

Mechanical cell competition kills cells via induction of lethal p53 levels.

Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults.

A genomic Multiprocess survey of machineries that control and link cell shape, microtubule organization, and cell-cycle progression.

Understanding cells as integrated systems requires that we systematically decipher how single genes affect multiple biological processes and how processes are functionally linked. Here, we used multiprocess phenotypic profiling, combining high-resolution 3D confocal microscopy and multiparametric image analysis, to simultaneously survey the fission yeast genome with respect to three key cellular processes: cell shape, microtubule organization, and cell-cycle progression. We identify, validate, and functionally annotate 262 genes controlling specific aspects of those processes.

Competitive cell interactions in cancer: a cellular tug of war.

Within tissues, cells sense differences in fitness levels and this can lead to fitter cells eliminating less fit, albeit viable, cells via competitive cell interactions. The involvement of several cancer-related genes in this phenomenon has drawn attention to a potential connection between competitive cell interactions and cancer. Indeed, initial studies found that tumor-promoting genes can turn cells into 'supercompetitors', able to kill normal cells around them.

Cell wars: regulation of cell survival and proliferation by cell competition.

During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels.

Steep differences in wingless signaling trigger Myc-independent competitive cell interactions.

Wnt signaling is a key regulator of development that is often associated with cancer. Wingless, a Drosophila Wnt homolog, has been reported to be a survival factor in wing imaginal discs. However, we found that prospective wing cells survive in the absence of Wingless as long as they are not surrounded by Wingless-responding cells.

Characterization of the interface between normal and transformed epithelial cells.

In most cancers, transformation begins in a single cell in an epithelial cell sheet. However, it is not known what happens at the interface between non-transformed (normal) and transformed cells once the initial transformation has occurred. Using Madin-Darby canine kidney (MDCK) epithelial cells that express constitutively active, oncogenic Ras (Ras(V12)) in a tetracycline-inducible system, we investigated the cellular processes arising at the interface between normal and transformed cells.

Interpretation of the wingless gradient requires signaling-induced self-inhibition.

In a classical view of development, a cell can acquire positional information by reading the local concentration of a morphogen independently of its neighbors. Accordingly, in Drosophila, the morphogen Wingless produced in the wing's prospective distal region activates target genes in a dose-dependent fashion to organize the proximodistal pattern. Here, we show that, in parallel, Wingless triggers two nonautonomous inhibitory programs that play an important role in the establishment of positional information.