Reviews & Analysis

The senescence-associated secretory phenotype (SASP) mediates the tissue effects of senescent cells. This Review discusses the composition, regulation and various biological implications of the SASP and its uses as a biomarker and a target of senomorphic drugs to treat cancer and other age-related conditions.

Tissues undergo changes in their mechanical and material properties through alterations in cytoskeleton organization, extracellular matrix adhesion and cell–cell connectivity. These mechanical state transitions orchestrate cell proliferation and movement and tissue growth during development, in adult tissue repair and in disease contexts.

Fibroblasts undergo transient activation into myofibroblasts to restore homeostasis to injured tissues. This Review explores the influence of mechanical cues and epigenetic modifications on (myo)fibroblast activation and memory and discusses potential therapeutic prevention of persistent myofibroblast activation in fibrosis.

Recent combinations of structure-based and sequence-based calculations and machine learning tools have dramatically improved protein engineering and design. Although designing complex protein structures remains challenging, these methods have enabled the design of therapeutically relevant activities, including vaccine antigens, antivirals and drug-delivery nano-vehicles.

This Review discusses the complex mechanisms of wound healing — cell migration, matrix remodelling, inflammation and angiogenesis — and the contributions of different cell types, including immune cells, to this process. It also highlights new methodologies that could inform future therapies to prevent scarring and repair chronic wounds.

Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.

Somite formation, crucial for organization of the segmental pattern of vertebrate embryos, depends on the oscillatory expression of segmentation clock genes. Novel in vitro models of somitogenesis have provided insights into the spatiotemporal dynamics of gene expression, signalling and metabolic gradients that enable somite formation and patterning.

Gene regulation in animals depends chiefly on enhancers, yet the underlying mechanisms are poorly understood. This Review discusses enhancer–promoter interactions and transcription activation, focusing on how enhancer–promoter selectivity is achieved and on recent technical advances that may provide new insights into transcription activation.

The prevailing challenge in live-cell fluorescence microscopy is capturing intra-cellular dynamics while preserving cell viability. Alongside developments of microscopy hardware, computational methods — especially those based on machine learning — are powerful tools to improve the signal-to-noise ratio, spatial resolution, temporal resolution and multi-colour capacity of live-cell imaging.

Cilia are microtubule-based cell projections that provide a unique environment with precise protein, lipid and second messenger concentrations, thereby creating specialized signalling hubs. This Review discusses recent multidisciplinary, mechanistic insights into cilia-based signalling pathways during development and homeostasis.

Ferroptosis is a non-apoptotic, iron-dependent cell death mechanism driven by plasma membrane lipid peroxidation and subsequent plasma membrane rupture. Various cellular compartments and organelles contribute to regulating susceptibility to ferroptosis. This regulation involves a plethora of mechanisms centred on iron metabolism and storage, lipid metabolism, and redox balance.

Protein S-acylation is involved in many pathophysiological processes. Here, Mesquita et al. discuss the structure, function and regulation of S-acylation and deacylation enzymes and describe how this post-transcriptional modification precisely controls protein–cell membrane interactions. Potential therapeutic applications of S-acylation are also highlighted.

L. Villiger, J. Joung et al. review CRISPR applications for programmable editing of the genome, epigenome and transcriptome. They discuss how CRISPR–Cas systems can be optimized to further improve editing specificity and efficiency and highlight a multitude of applications in basic biological research and for changing clinical practice.

This Review discusses the emerging roles of long non-coding RNAs (lncRNAs) in the regulation of transcription, for example by controlling the expression of transcription factors. Some lncRNA loci function in trans, but most function in cis, through their own transcription or through the lncRNA transcripts themselves.

tRNA-derived small RNAs (tdRs) have long been considered mere intermediates of tRNA degradation. This Review discusses the biogenesis and regulation of tdRs and focuses on their emerging gene regulation roles in cell metabolism, immune responses, development and cancer.

The Rho GTPases are small GTP binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. These different functions are driven by the ability of Rho GTPases to self-organize, forming diverse spatiotemporal cortical patterns.

Cell death can result from the activation of dedicated programmed cell death machineries or disruption of pro-survival mechanisms. This Review describes the different major mechanisms of cell death and discusses recent insights into their relevance to disease.

Scientists are captivated by the prospect of creating a fully synthetic cell, offering the potential to revolutionize biology, medicine and biotechnology. In this Viewpoint, a panel of experts discusses the definitions of a synthetic cell and highlights current achievements, challenges and future opportunities of building such systems.

Plant cells assemble a strong yet extensible primary cell wall consisting largely of polysaccharides. Emerging models of wall growth integrate physical properties such as mechanical strength and tension with cellular processes that govern wall loosening and expansion.

Adherens junctions (AJs) are canonical mediators of cell–cell adhesion that support embryonic development and tissue homeostasis. This Review discusses how the properties and behaviours of embryonic tissues emerge from the collective molecular interactions that occur at AJs.