Browse Articles

This issue presents a Focus of specially commissioned articles that discuss cell death in its multiple forms, implications for homeostatic physiology and disease and outstanding questions in this expanding field.

Hao, Shen and colleagues identify and characterize two distinct types of myeloid–B cell interaction that may signal solid tumour-induced immunosuppression and can correlate with complete responses to immunotherapy in patients with breast cancer.

Combining degron-based depletion with live-cell transcription imaging and single-particle tracking, Szczurek et al. show that Polycomb keeps promoters in an OFF state by restricting the formation of the pre-initiation complex.

Zhang, Liu and colleagues identify and characterize cell death in rapidly proliferating CD8⁺ T cells resulting from excessive ammonia accumulation and subsequent lysosomal dysfunction and mitochondrial damage.

Schliffka et al. show that in the early mouse embryo, hemispherical intrusions, or inverse blebs, grow into cells at cell–cell adhesion sites in response to luminal fluid accumulation and pressure build-up, and may serve as pumps moving fluid into hydraulic sinks.

Guo, Hong et al. report that TET2 condensation maintains proper DNA demethylation at specific genomic loci, which can be targeted to alter gene expression and impair leukaemia growth.

de Caestecker and Macara study apical sorting of proteins with varying cytoplasmic tail length in epithelial cells. They propose that a size filter at the Golgi facilitates apical sorting of proteins with small cytoplasmic domains.

Tamagawa, Fujii et al. demonstrate that squamous differentiation in human pancreatic cancer can be attributed to TP63-mediated lineage conversion and epigenetic reprogramming that depends upon a hypoxic and Wnt-defective niche.

The tumour microenvironment propagates stress responses in resident cells. In tumour-infiltrating natural killer (NK) cells, the HSF1 transcription factor binds to mediators of effector function, negatively regulating NK cytotoxicity. These findings provide important mechanistic insights that may enhance NK cell cancer therapy.

Pluripotent stem cells are being used to generate models of early embryogenesis that are promising for discovery and translational research. To be useful, these models require critical consideration of their level of efficiency and fidelity to natural embryos. Here we propose criteria with which to raise the standards of stem-cell-based embryo models of human embryogenesis.

Hockemeyer et al. demonstrate that HSF1 activation inhibits cytokine production and cytotoxic activity in NK cells to impair anti-tumour immune responses.

Man and Kanneganti discuss how pattern-recognition sensors in innate immune cells recognize and respond to cell-death signatures, and highlight molecular targets for potential therapeutic development.

Eroglu et al. describe protein amyloid structures that are stably inherited across generations and transmit epigenetic memory in Caenorhabditis elegans. MSTR protein loss results in a transgenerational feminization phenotype through ectopic GLD-1 expression.

Dimitrov et al. present LIANA+, a framework that unifies and extends approaches to study inter- and intracellular signalling from diverse mediators, captured from single-cell, spatially resolved and multi-omics data.

Cao et al. describe the development and application of an engineered protein system (MARS) derived from PLEKHA5 that allows mitosis-specific recruitment of proteins to the plasma membrane to study protein function in cell division.

Park et al. show that cells with impaired autophagy shuttle cytoplasmic proteins to the nucleus for degradation by nuclear proteasomes, revealing synergistic vulnerabilities in diseases where autophagy and nucleocytoplasmic transport are compromised.