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Lineage transitions are a central feature of prostate development, tumorigenesis and treatment resistance. We discovered that inhibition of mitochondrial pyruvate uptake results in large-scale chromatin remodelling of key lineage-specific genes, antagonizes luminal lineage identity, and alters response to antiandrogen therapy in prostate cancer.

Lineage plasticity and epigenetic changes underlie prostate development and cancer evolution. A new study shows that basal and luminal prostate cells have distinct metabolic profiles, with a basal-to-luminal shift intensifying pyruvate oxidation. Metabolic changes in turn influence chromatin architecture, lineage reprogramming and treatment sensitivity.

Giafaglione et al. define metabolic regulation of prostate epithelial lineage identity and show that modulation of lactate metabolism alters response to antiandrogen therapy.

Gerber-Ferder et al. show that non-metastatic breast tumours remotely reprogram the bone marrow stroma and instruct the myeloid differentiation of long-term haematopoietic stem cells.

There is increasing interest in approaches that target and eliminate senescent cells. A study reports that the coatomer complex I (COPI) pathway is important for the survival of senescent cells, and suggests that targeting this pathway could hold therapeutic promise in the context of senescence-associated diseases.

Gao et al. report that leptin receptor⁺ stromal cells sustain nerves in the bone marrow by producing nerve growth factor. After myeloablation, nerves promote marrow regeneration by increasing the production of multiple growth factors by leptin receptor⁺ cells.

McHugh et al. identify COPI trafficking as a vulnerability of senescent cells. N-myristoyltransferase inhibitors phenocopy COPI inhibition and are potent senolytics.

Noack and Vangelisti et al. present 3DRAM-seq, which simultaneously profiles genome organization, chromatin accessibility and DNA methylation at high resolution and allows mapping cell-type-specific epigenetic regulation in human neurogenesis.

Cell death is an important biological process whose experimental detection and measurement can be difficult, especially when examining many conditions in parallel. The interpretation of cell death data is complicated by the diversity of measurement techniques and lack of standardized methods in the field. Here, we offer tips to help interpret cell death experiments.

Human embryology is flourishing thanks to an impetus provided by embryo models formed from stem cells. These scientific advances require meticulous experimental work and a refined ethical framework, but also sensible public communication. Securing public support is essential to achieve societal impact.

By regulating the condensation of the molecular transport machinery coat protein complex II (COPII), manganese ions contribute to the regulation of lipoprotein secretion and thereby the circulating lipid levels.

The main barriers for intracellular receptors to sense circulating pathogen-associated molecular patterns (PAMPs) is how these PAMPs enter the cells. A study reveals that extracellular vesicles (EVs) bind lipopolysaccharide (LPS) via the lipid bilayer and mediates LPS intracellular transfer in a CD14-dependent endocytosis to activate noncanonical NLRP3 inflammasome and pyroptosis.

Kumari et al. show that host-derived extracellular vesicles capture systemic LPS and transfer it to the cytosol of immune cells via CD14-dependent endocytosis, triggering caspase-11-mediated gasdermin D activation and pyroptosis.

Evans, Blake, Longworth and colleagues identify and characterize a tumour-suppressive role for microglia that mediate a pro-inflammatory response to restrict brain metastasis in breast cancer.

Munk et al. show that exogenous NAD⁺, but not its precursors, induces metabolic changes in mitochondria affecting nucleotide metabolism with impacts on genomic DNA synthesis and genome integrity.