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Son et al. show that AMPK- and PP2A-dependent p300 nucleocytoplasmic shuttling regulates mTORC1 activity in response to nutrient status. Models of Hutchinson–Gilford progeria syndrome display increased cytoplasmic p300 and mTORC1 hyperactivation.
Huang, Qin, Shang et al. profile double-strand breaks (DSBs) generated by C-to-G base editors (CGBEs) and find that HMCES protects abasic sites and reduces CGBE-triggered DSBs.
Lin Li, Lei Li et al. perform single-cell multi-omics to study the transcriptome, the DNA methylome and chromatin accessibility in human arrested embryos and find that cytoskeletal defects cause embryonic arrest characterized by zygotic genome activation.
Joyce, Pascual et al. identify luminal progenitors as likely cells-of-origin in BRCA2-mutant breast cancer, exhibiting dysregulated proteostasis and translation, which may be therapeutically targeted via mTORC1 inhibition.
Reverte-Salisa et al. show that, in preadipocytes, EPAC1 enhances brown adipose tissue growth and increases the function of thermogenic fat in obesogenic conditions. Activation of EPAC1 induces human brown adipocyte proliferation and differentiation.
Using modification-induced misincorporation tRNA sequencing, Gao and Behrens find that on differentiation, reduced mTORC1 signalling activates MAF1, which restricts RNA polymerase III to human tRNA housekeeping genes, to ensure that tRNA anticodon pools remain stable.
Bravo González-Blas et al. uncover enhancer-gene regulatory networks underlying hepatocyte identity and their zonation state by combining single-cell and spatial multiomics with massively parallel reporter assays and deep learning.
van der Weijden et al. perform genomic, proteomic and metabolic analyses and find that FOXO1-mediated fatty acid oxidation maintains mouse embryos in diapause.
Shao et al. report that FUS interacts with the transcriptional coactivator TAZ, maintaining liquid-like properties of TAZ biomolecular condensates and enhancing TAZ transcriptional activity.
Sissoko et al. show that CENP-T local concentration regulates its ability to recruit the outer kinetochore, which may restrict complete kinetochore formation to regions with higher-order inner kinetochore assemblies.
Cui, Guo, Liu et al. identify a bacterial species, Peptostreptococcusanaerobius, in the gut that produces a tryptophan metabolite and engages intracellular pathways to modulate ferroptosis-suppressor protein 1 activity, thereby suppressing ferroptosis and promoting colorectal cancer development.
Kang et al. find that vitamin B12 from gut bacteria modulates host neural function and behaviour in Caenorhabditis elegans: vitamin B12 rewires the methionine/S-adenosylmethionine cycle and choline metabolism, impacting free choline levels for neuronal acetylcholine synthesis.
Lee et al. use three-dimensional cell reconstruction of focused ion beam scanning electron microscopy data and multi-omics to show that ether-lipid metabolism regulates inter-organelle biogenesis and dynamics.
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.
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.
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.