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Healthy and malignant haematopoietic stem cells (HSCs) must overcome a variety of cell intrinsic and extrinsic stresses to maintain their functionality. Now, IRE1α –XBP1 signalling is shown to protect HSCs and to promote survival of, and confer competitive advantages to, NRAS-mutated pre-leukaemic cells.
Epithelial–mesenchymal transition (EMT) is crucial for development, and for dissemination and invasion of cancer cells. A study now identifies the apical–basolateral polarity status of epithelia as a checkpoint for EMT induction and tumour metastasis through aPKC–Par3-regulated degradation of the EMT transcription factor SNAI1.
Cell metabolism ensures that cell dynamics and continued renewal are supported by a constant flow of matter that consumes energy. A new study shows that cell metabolism is sensitive to mechanical cues, revealing that the level of cell contraction modulates the production and storage of lipids, which could serve as fuel for energy production.
Ancestral experience of mitochondrial stress is now found to render progeny of the roundworm Caenorhabditis elegans more resistant to the same insult for up to four generations. A DNA modification, N6-methyldeoxyadenine, is implicated in the inheritance of this stress adaptation.
Kraft et al. show that chromosomal inversions that relocate a limb enhancer can establish asymmetric stripes of the enhancer with downstream genes, resulting in ectopic gene expression and limb phenotypes.
Nakamura et al. show that DNA repair pathway choice and initiation of homologous recombination is guided by the recruitment of BRCA1 to post-replicative chromatin by BARD1 recognition of histone H4 tails unmethylated on lysine 20.
Ma et al. show that exposure of Caenorhabditis elegans to mitochondrial stress triggers stress adaptation in offspring, which is mediated by 6mA DNA modification at mitochondrial unfolded-protein-response genes.
Liu et al. show that the adaptive branch of unfolded protein response signalling, IRE1α–XBP1, protects haematopoietic stem cells and N-Ras pre-leukaemic stem cells from endoplasmic reticulum stress-induced apoptosis and supports their self-renewal.
Romani et al. identify a response to reduced actomyosin contractility involving inhibition of Lipin-1, accumulation of SREBP transcription factors at the Golgi apparatus and activation of SREBP transcription driving increased lipid synthesis.
Moro et al. discover an Argonaute 2 (Ago2)-dependent miRNA network that, in response to substrate stiffness, regulates genes involved in tissue mechanics, and show that Ago2 restrains stiffness and contributes to regeneration in the zebrafish fin fold.
Jung et al. demonstrate, using 3D organoid cultures, that the PAR–aPKC polarity complex counteracts epithelial–mesenchymal transition and invasion through phosphorylation-dependent regulation of SNAI1 stability.
Lystad et al. identify distinct membrane binding regions in ATG16L1 and show that the β-isoform-specific C-terminal region is required for VPS34/ULK1/2-independent non-canonical autophagy.
Şentürk et al. show that ubiquilins bind v-ATPase to control lysosome acidity, mTOR signalling and autophagic flux in neurons, and that feeding flies with acidic nanoparticles ameliorates defective autophagy in ubiquilin mutants.
Nacarelli et al. show that the nicotinamide-phosphoribosyltransferase-regulated NAD+ biogenesis pathway promotes the proinflammatory senescence-associated secretory phenotype by enhancing glycolysis and mitochondrial respiration during senescence.