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.

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.

Gasdermins are a family of proteins that form membrane pores and elicit pyroptosis. This Review discusses recent work highlighting their regulation and emerging biological roles, including in non-lethal pore formation and host defence.

The subcellular localization of numerous mRNAs has been demonstrated. This Review presents the different means of mRNA localization described and discusses how they can account for the widespread occurrence of this phenomenon.

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.

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.

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.