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During early mouse development, a fluid-filled lumen inflates the embryo. Membrane protrusions called inverse blebs have been found to form at cell–cell contacts. Cycles of inverse bleb filling and unloading act as hydraulic pumps and contribute to the formation of the lumen.
Yuzhalin et al. report that astrocyte-mediated upregulation of Cdk5 in metastatic breast cancer cells inhibits MHC-I expression on the cell surface, thereby enabling escape from killing by CD8+ T cells and facilitating brain metastasis.
Al-Refaie et al. show that fasting induces spatial reorganization of chromatin and formation of chromatin rings in an mTORC1- and RNA Pol I-dependent manner in the C. elegans intestine.
Xu, Liang, Li, Dang et al. delineate the clathrin-associated fast endosomal recycling pathway, which involves clathrin-associated carriers derived from early endosomes partially fusing with the plasma membrane before release from the membrane.
Yang et al. show that plasma membrane curvature promotes the site-specific formation of contacts with the endoplasmic reticulum through junctophilin-2 tethers in cardiomyocytes.
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.