Although tumor protein p53 (TP53) mutations are among the most common lesions in epithelial cancers, how p53 loss drives unrestrained clonal expansion remains unclear. Working with mouse epidermis, we...

Ribosomal RNA (rRNA) transcription rates vary during development, and their dysregulation is linked to diseases such as cancer and ribosomopathies. Owing to their high abundance and genomic redundancy...

Cell-state diversity drives tissue adaptability, repair, and disease resilience, but capturing this complexity is a challenge. Current approaches rely on transcriptional profiling and overlook organel...

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Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Although current therapies aim to cor...

Suppressor transfer RNAs (sup-tRNAs) can rescue disease-causing nonsense mutations by promoting readthrough of premature termination codons (PTCs). Their clinical translation is limited by suboptimal ...

Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover vi...

Dystroglycan (DG) is an extracellular matrix receptor crucial for tissue development and pathogen entry. DG harbors a long, complex glycan called matriglycan. Loss of matriglycan or reduction in its l...

The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanis...

Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo d...

The metabolite α-ketoglutarate (αKG) is required for chromatin demethylation, but mechanisms that control αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metab...

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Impairments in intracellular quality-control mechanisms, including autophagy, affect neuronal integrity and function. Despite numerous studies aimed at slowing neuronal deterioration, it remains uncle...

Stratified epithelial differentiation involves transcriptional and proteomic remodeling. Here, multiomic profiling implicated ubiquitin and related posttranslational networks in differentiation dynami...

The exchange of biological matter between bacterial cells drives adaptation and evolution. However, whether bacteria can exchange functional proteins remains unclear. In this work, we found that antib...

During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the ma...

The adult heart grows by the addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. We found that microtubu...

The adult heart grows by addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. Here, we found that microtu...

Bacteria, like eukaryotes, use conserved cytoskeletal systems for intracellular organization. The plasmid-encoded ParMRC system forms actin-like filaments that segregate low–copy number plasmids. In m...

Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, ...

Why mammals cannot regenerate limbs like amphibians do presents a long-standing puzzle in biology. To uncover the underlying differences, we compared amputation responses of embryonic mouse (Mus musculus) and Xenopus laevis tadpole limbs. Lowering ...

The distribution of mitochondrial DNA–containing nucleoids is essential for mitochondrial function and genome inheritance; however, no known mechanisms can explain nucleoid segregation or their regula...

The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15BR...

One defining feature of complex organisms is the ability to maintain protein homeostasis beyond cellular boundaries. We review how extracellular proteostasis is organized as a hierarchical network spa...

Chronic kidney disease (CKD) is linked to an elevated fecal abundance of Enterobacteriaceae, but the ecological drivers of this shift and its impact on disease progression remain unclear. The uremic t...

Altered metabolism is a hallmark of cancer: malignant cells re-engineer nutrient acquisition and utilization to fuel unchecked growth and survival. Beyond functioning as a simple energy powerhouse, me...

Overexpression of the proto-oncogene Src is common to a wide variety of cancers. In this work, we found that Src is noncanonically translocated and inverted onto the cell surface in cancer, both in vi...

Gene expression patterns underlie development, but their systematic detection in whole embryos has remained elusive. We introduce a whole-embryo imaging platform using multiplexed error-robust fluores...

Altered metabolism is a hallmark of cancer: malignant cells re-engineer nutrient acquisition and utilization to fuel unchecked growth and survival. Beyond functioning as a simple energy powerhouse, metabolic rewiring reshapes virtually every layer of cell regulation, from chromatin architecture a...

Stress responses enable cells to detect, adapt to, and survive challenges. The benefit of these signaling pathways depends on their reversibility. The integrated stress response (ISR) is elicited by p...