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Chandrakanthan et al. identify Mesp1-derived PDGFRA+ stromal cells as aortic endothelial precursors that regulate long-term haematopoietic-stem-cell generation during development, thus providing a new potential tool to generate engraftable haematopoietic stem cells.
Using single-cell analysis, Tan et al. map the cellular and spatial hierarchy and heterogeneity of eutopic endometrium and characterize ectopic peritoneal and ovarian endometriosis lesions from individuals receiving hormone treatment.
Hao et al. describe an RNA-editing-independent role for ADAR1 in driving senescence. Autophagy downregulates ADAR1 in aged tissues, decreasing the binding of ADAR1 partner HuR to target mRNAs, including SIRT1. Loss of SIRT1 enhances p16INK4a levels.
Lin, Swedlund et al. report that Mesp1 governs the remodelling of the chromatin and enhancer landscape during differentiation of early mesodermal cells into distinct populations of cardiovascular progenitors.
Emam et al. report that Abro1 and FANCD2 protect stalled replication forks from degradation, thereby preventing the accumulation of cytosolic ribosomal DNA and the activation of cGAS–STING- and P-body-dependent innate immune responses.
Mylvaganam et al. report that an apical spectrin network in endothelial cells can transmit mechanical forces in response to shear flow-induced stress, requiring hyaluronic acid and involving PIEZO1.
Chen et al. report that following genotoxic stress, a nuclear PI3K binds p53 to generate a p53–phosphoinositide signalosome that recruits AKT and its activators, resulting in nuclear AKT activation and cell survival.
Yang et al. report that HHEX acts as a gatekeeper of pancreatic lineage specification against the liver and duodenum fates via guiding FOXA1, FOXA2 and GATA4 to activate pancreatic genes, while restraining them from activating alternative lineages.
Meng et al. show that ZBTB43 alters Z-DNA structures to prevent deleterious double-strand breaks and promote DNA methylation at purine–pyrimidine repeats in the mouse germ line.
Zhu et al. identify Dapl1 as a negative regulator of CD8+ T cell responses by modulating NFATc2 activation and T cell exhaustion, leading to dysregulated control of chronic infection and cancer.
Williams et al. report that, upon TORC1 inhibition in yeast, mRNA of the chaperone protein ADC17 is localized to cortical actin patches where its translation is enhanced upon stress.
Ouyang et al. show that the RNA helicase ZNFX-1 preserves heritable RNAi by maintaining a pool of small RNA-targeted transcripts in perinuclear condensates of the Caenorhabditiselegans germline, which serve as templates for small-RNA amplification in the next generation.
Arya et al. identify a pathway for exosome generation in immune cells that originates at the nuclear envelope and is facilitated by nSMase1-mediated generation of ceramide.
Haque et al. report that the Hedgehog pathway kinesin KIF7 binds the transcription factor GLI via electrostatic coiled-coil interactions, and synergy between KIF7 and GLI underlies the recruitment of both proteins to microtubules and the cilium tip.
Zhang et al. use single-cell RNA sequencing and functional analyses to describe the hyaluronic acid–GPRC5C signalling axis as an essential component controlling the state of dormancy for human and mouse haematopoietic stem cells.
Zhang et al. identify that a group of PP2C phosphatases is responsible for direct sensing of CO2 in the environment via phase separation of an intrinsically disordered region, which is a conserved mechanism across various species.
Using an optimized Ribo-seq protocol that is applicable for low-input samples, Xie, Li and colleagues revealed the translation landscape during oocyte-to-embryo transition and in pre-implantation embryos.
Rosebrock, Arora et al. report a method to overcome limited cortical cellular diversity in human organoids, thus mirroring fundamental features of cortical development and offering a basis for organoid-based disease modelling.
Two side-by-side papers report that H3K27me3 deposited by polycomb repressive complex 2 represents an epigenetic barrier that restricts naive human pluripotent cell differentiation into alternative lineages including trophoblasts.