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Volume electron microscopy (vEM) generates large 3D volumes of cells or tissues at nanoscale resolutions, enabling analyses of organelles in their cellular environment. Here, we provide examples of vEM in cell biology and discuss community efforts to develop standards in sample preparation and image acquisition for enhanced reproducibility and data reuse.
Chidley et al. report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments of variable composition.
When transcription by RNA polymerase II is stalled by ultraviolet-induced DNA damage, it recruits repair factors, leading to excision of the damaged site and DNA synthesis to fill the gap. Three new studies show that, for aldehyde-induced DNA crosslinks, repair is activated by the same factors, but without base excision and gap filling.
Organ morphogenesis begins with proliferation, which results in tissue pressures and site-specific YAP expression, nuclear translocation and signalling. A study now reports the involvement of anisotropy, localized pressure and YAP signalling in organizer-forming cascades, introducing a new chapter of molecular mechanobiology of organogenesis.
Three studies identify a transcription-coupled DNA–protein cross-link repair pathway that depends on the Cockayne syndrome proteins and the proteasome.
Liu et al. find that long-chain acyl-coenzyme A activates two mitochondrial fission proteins, MiD49 and MiD51, by inducing their oligomerization. This activates their ability to stimulate DRP1 GTPase activity and triggers mitochondrial division.
Scarfò, Randolph et al. perform transcriptomic analysis of 28- to 32-day human embryos and identify CD32 as a marker of haemogenic endothelial cells (HECs), thus providing a strategy to isolate HECs from human embryos and pluripotent stem cell cultures.
Eukaryotic transcriptional machinery often shows local enrichment in dynamic clusters at sites of high expression. A study of zebrafish embryos shows that such clusters can fine-tune the timing of zygotic genome activation by sequestering a component required for productive transcription, thus limiting its availability to other genes.
Diverse, specialized immune cells defend against pathogens and cancer cells. A new study reveals the comprehensive lipid compositions of these cells, with unique lipidomes associated with various immune cell types. They show that cell-specific lipid compositions determine a key functional phenotype: their susceptibility to ferroptosis.
Morgan, Pernes and colleagues perform mass spectrometry-based targeted lipidomics and provide a comprehensive lipid profile of human and mouse immune cells, which they then show confer differential ferroptosis susceptibilities.
Ugolini et al. show that transcription bodies regulate gene expression during zygotic genome activation in zebrafish development by sequestering CDK9 to limit the transcription of genes away from transcription bodies.
Shroff and colleagues report that cell proliferation induces localized mechanical compression in the tissue, driving the formation of the main mouse tooth signalling centre via differential YAP expression.
Maneix, Iakova and colleagues report that cyclophilin A is a chaperone for, and regulator of, intrinsically disordered proteins within haematopoietic stem and progenitor cells, with potential effects on ageing-like phenotypes and lineage commitment.
Using single-molecule tracking and spatiotemporal mapping, Ling et al. show that the C-terminal domain of RNA polymerase II facilitates its dynamic confinement in subnuclear regions enriched in active genes, where it promotes targeted transcription.
Coquand, Brunet Avalos et al. develop an imaging method to map basal radial glial cell division in human fetal tissue and cerebral organoids and detect abundant symmetric amplifying, but also direct neurogenic divisions bypassing intermediate progenitors.
Progeria, or premature ageing, is a devastating condition caused by defects in the nuclear envelope and is associated with systemic inflammation. A study now shows in animal models that inhibiting necroptosis, and particularly activity of the RIPK1 kinase, reduces inflammation and results in a meaningful extension in lifespan1.