Trends in Cell Biology最新文献

Neutrophils have recently received increased attention in cancer because they contribute to all stages of cancer. Neutrophils are so far considered to have a short half-life. However, a growing body of literature has shown that tumor-associated neutrophils (TANs) acquire a prolonged lifespan. This review discusses recent work surrounding the mechanisms by which neutrophils can persist in the tumor microenvironment (TME). It also highlights different scenarios for therapeutic targeting of protumorigenic neutrophils, supporting the idea that, in tumors, inhibition of neutrophil recruitment is not sufficient because these cells can persist and remain hidden from current interventions. Hence, the elimination of long-lived neutrophils should be pursued to increase the efficacy of standard therapy.

Metazoan organisms are heterocellular systems composed of hundreds of different cell types, which arise from an isogenic genome through differentiation. Cellular 'plasticity' further enables cells to alter their fate in response to exogenous cues and is involved in a variety of processes, such as wound healing, infection, and cancer. Recent advances in cellular model systems, high-dimensional single-cell technologies, and lineage tracing have sparked a renaissance in plasticity research. Here, we discuss the definition of cell plasticity, evaluate state-of-the-art model systems and techniques to study cell-fate dynamics, and explore the application of single-cell technologies to obtain functional insights into cell plasticity in healthy and diseased tissues. The integration of advanced biomimetic model systems, single-cell technologies, and high-throughput perturbation studies is enabling a new era of research into non-genetic plasticity in metazoan systems.

To face genotoxic stress, eukaryotic cells evolved extremely refined mechanisms. Defects in counteracting the threat imposed by DNA damage underlie the rare disease Cockayne syndrome (CS), which arises from mutations in the CSA and CSB genes. Although initially defined as DNA repair proteins, recent work shows that CSA and CSB act instead as master regulators of the integrated response to genomic stress by coordinating DNA repair with transcription and cell division. CSA and CSB exert this function through the ubiquitination of target proteins, which are effectors/regulators of these processes. This review describes how the ubiquitination of target substrates is a common denominator by which CSA and CSB participate in different aspects of cellular life and how their mutation gives rise to the complex disease CS.

Bleb-based migration, a conserved cell motility mode, has a crucial role in both physiological and pathological processes. Unlike the well-elucidated mechanisms of lamellipodium-based mesenchymal migration, the dynamics of bleb-based migration remain less understood. In this review, we highlight in a systematic way the establishment of front-rear polarity, bleb formation and extension, and the distinct regimes of bleb dynamics. We emphasize new evidence proposing a regulatory role of plasma membrane-cortex interactions in blebbing behavior and discuss the generation of force and its transmission during migration. Our analysis aims to deepen the understanding of the physical and molecular mechanisms of bleb-based migration, shedding light on its implications and significance for health and disease.

Targeting RNA m⁶A marks in apoptosis-related transcripts holds promise for RNA therapeutics. However, pathway-specific RNA m⁶A sites on pro- or antiapoptotic transcripts have not been fully unveiled, let alone characterized. This article summarizes the current knowledge and gaps in the cellular response modulated by apoptotic stimulus-specific RNA m⁶A marks.

Enhancers are noncoding regulatory elements that instruct spatial and temporal specificity of gene transcription in response to a variety of intrinsic and extrinsic signals during development. Although it has long been postulated that enhancers physically interact with target promoters through the formation of stable loops, recent studies have changed this static view: sequence-specific transcription factors (TFs) and coactivators are dynamically recruited to enhancers and assemble so-called transcription hubs. Dynamic assembly of transcription hubs appears to serve as a key scaffold to integrate regulatory information encoded by surrounding genome and biophysical properties of transcription machineries. In this review, we outline emerging new models of transcriptional regulation by enhancers and discuss future perspectives.

The Stimulator of Interferon Genes (STING) has a crucial role in mediating the immune response against cytosolic double-stranded DNA (dsDNA) and its activation is critically involved in various diseases. STING is synthesized, modified, and resides in the endoplasmic reticulum (ER), and its ER exit is intimately connected with its signaling. The ER, primarily known for its roles in protein folding, lipid synthesis, and calcium storage, has been identified as a pivotal platform for the regulation of a wide range of STING functions. In this review, we discuss the emerging factors that regulate STING in the ER and examine the interplay between STING signaling and ER pathways, highlighting the impacts of such regulations on immune responses and their potential implications in STING-related disorders.

Cell surface and intracellular mechanosensors enable cells to perceive different geometric, topographical, and physical cues. Mechanosensitive ion channels (MICs) localized at the cell surface and on the nuclear envelope (NE) are among the first to sense and transduce these signals. Beyond compartmentalizing the genome of the cell and its transcription, the nucleus also serves as a mechanical gauge of different physical and topographical features of the tissue microenvironment. In this review, we delve into the intricate mechanisms by which the nucleus and different ion channels regulate cell migration in confinement. We review evidence suggesting an interplay between macromolecular nuclear-cytoplasmic transport (NCT) and ionic transport across the cell membrane during confined migration. We also discuss the roles of the nucleus and ion channel-mediated mechanosensation, whether acting independently or in tandem, in orchestrating migratory mechanoresponses. Understanding nuclear and ion channel sensing, and their crosstalk, is critical to advancing our knowledge of cell migration in health and disease.

The tumor microenvironment (TME) is a complex and heterogeneous system containing various cells cooperating and competing with each other. Extracellular vesicles (EVs) differing in form and content are important intercellular communication mediators in the TME. Previous studies have focused on the cargoes within EVs rather than on the donors from which they originate and the recipient cells that exert their effects. Therefore, we provide here a detailed overview of the important roles of EVs in shaping tumor fate, highlighting their various mechanisms of intercellular dialog within the TME. We evaluate recent advances and also raise unresolved challenges to provide new ideas for clinical treatment strategies using EVs.

Hematopoietic stem cells (HSCs) sustain blood cell production throughout the mammalian life span. However, it has become clear that at the single cell level a subset of HSCs is stably biased in their lineage output, and that such heterogeneity may play a key role in physiological processes including aging and adaptive immunity. Analysis of chromatin accessibility, DNA methylation, and histone modifications has revealed that HSCs with different lineage bias exhibit distinct epigenetic traits inscribed at poised, lineage-specific enhancers. This allows for lineage priming without initiating lineage-specific gene expression in HSCs, controlling lineage bias while preserving self-renewal and multipotency. Here, we review our current understanding of epigenetic regulation in the establishment and maintenance of HSC fate decisions under different physiological conditions.