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Meng et al. show that the RNA polymerase II elongation factor ELL3 suppresses the 5′ untranslated region activities of a subset of young LINE-1 elements, which activate genes such as Akt3, and regulate ERK signalling and naïve pluripotency in mouse embryonic stem cells.
Nicastro, Brohée et al. find that the fatty acid synthesis intermediate malonyl-CoA inhibits mTORC1, showing mTORC1 senses the capacity of a cell to synthesise fatty acids and linking fatty acid generation with the overall biosynthetic output through mTORC1.
Wang et al. show that intestinal sphingosine-1-phosphate is transferred to oocytes and influences sphingolipid metabolism in the next generations. In the offspring, sphingosine-1-phosphate protects Caenorhabditis elegans neurons against axon fragility.
Yang, Gomez et al. show that the pioneer factor SOX9 regulates the switch from epidermal stem cell to hair follicle stem cell fate by binding and opening hair follicle enhancers, while recruiting epigenetic factors away from epidermal enhancers.
Liang et al. report mechanisms of migrasome biogenesis in migrating cells. They propose that sphingomyelin synthase 2 (SMS2) is required for migrasomes, first by localizing in stable puncta where they eventually form migrasome structures.
Hoetker et al. show that H3K36 methylation exerts a dual role in cell identity maintenance: it integrates TGFβ signals at mesenchymal targets to keep them active and prevents the activation of alternative lineage programmes via enhancer methylation.
Ghersi et al. report that haematopoietic stem and progenitor cell heterogeneity is established on the haemogenic endothelium level and is, at least in part, regulated by microRNA-128-mediated modulation of Wnt and Notch signalling.
Dai et al. show that the transcription factor ATFS-1 interferes with mitochondrial pre-initiation transcription complex assembly and promotes mitochondrial DNA repair, thereby reducing age-dependent mitochondrial DNA damage in Caenorhabditiselegans.
Chen, Neil, Tan, Rudraraju et al. use an induced trophoblast stem-cell-based model of SARS-CoV-2 infection and identify syncytiotrophoblasts as the cells targeted by the virus in the early placenta.
Chung et al. identify the protein spartin, linked to Troyer syndrome, as a lipophagy receptor for lipid droplet clearance in vitro and in vivo. The data suggest that impaired lipid droplet turnover may contribute to Troyer syndrome development.
Zhang, Jiang and colleagues demonstrate that, independent of its role in innate immunity, STING can target and inhibit HK2 activity, thereby blocking tumour aerobic glycolysis and enhancing antitumour immune responses.
Alkhoury et al. show that the class 3 phosphatidylinositol-3-kinase Vps15 subunit coactivates the circadian clock transcription factor Bmal1–Clock for metabolic rhythmicity in the liver and promotes pro-anabolic de novo purine synthesis.
Gaggioli, Lo et al. show that the histone methyltransferase EHMT2/G9a catalyses heterochromatin assembly at stressed replication forks. Untimely heterochromatin disassembly by demethylase KDM3A exposes forks to PRIMPOL-mediated genome instability.
Zhang, Xu, Liu, Wang et al. identify an inhibitory mechanism for RIPK1 kinase through EGLN1/pVHL-mediated proline hydroxylation, which is disrupted upon prolonged hypoxia that activates RIPK1 activity to promote cell death and inflammation.
Enkler et al. show that a pool of Arf1 at lipid droplets is implicated in mitochondrial ATP production control through regulation of fatty acid metabolism and acetyl-CoA transfer to mitochondria.
Gao, Mathur, Tam and colleagues characterize transcriptomic and epigenomic alterations at the maternal–fetal interface in patients with COVID-19, thereby providing insights into aberrant pregnancy outcomes associated with SARS-COV-2 infection.
Martinez-Lopez et al. show that fasting or lipid availability stimulates mTORC2 activity in the liver, leading to phosphorylation of NDRG1 and NDRG1–CDC42-mediated mitochondrial fission.
Through a genome-wide CRISPR synthetic viability screen for PARP-inhibitor resistance, Chen and Ge et al. show that transmembrane nuclease NUMEN directs double-stranded DNA break repair pathway choice at the nuclear periphery.
Ton, Keitley et al. provide a morphological and molecular atlas of rabbit development. Comparative studies reveal that combining rabbit and mouse atlases can serve as a model for dissecting early primate development.