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Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.

Endothelial cells play a critical role in the adaptation of tissues to injury and show a remarkable plasticity. Here the authors show, using single cell sequencing, that endothelial cells acquire a transient mesenchymal state associated with metabolic adaptation after myocardial infarction.

Here, Reader et al. screen the Medicines for Malaria Venture Pandemic Response Box in parallel against Plasmodiumasexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. They identify two potent transmission-blocking drugs: a histone demethylase inhibitor ML324 and the antitubercular SQ109.

Roesch and colleagues use clinical datasets and mouse models of BRAF-mutant melanoma to reveal a role for IL-17A in positive responses to anti-PD-1 and anti-CTLA-4 therapy, which they also link to infiltrating neutrophils.

Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children.

The egg membrane protein Bouncer is an important mediator of gamete interaction and prevents cross-fertilisation between medaka and zebrafish. This study demonstrates unique functional and structural differences in Bouncer proteins of these and other distantly related fish species which may determine which species can hybridize.

The role of histone mutations in leukemogenesis remains largely unexplored. In this study of AML, the authors show that histone mutations are early events that drive a more aggressive phenotype.

Fernández-Chacón et al. use imaging and scRNA-seq after targeting multiple Notch genes and angiogenic signaling pathways to find that the function of these pathways in vascular pathophysiology cannot be predicted by assessing transcriptional states.

The synthesis of NPY and its receptor Y1R increases in lung phagocytes during severe influenza virus infection, leading to the induction of SOCS3 and impaired antiviral response and increased pro-inflammatory cytokine production.

The presence of an accessory genetic element, tarIJLM—which leads to the production of a S. aureus-type wall teichoic acid—alters the lifestyle of S. epidermidis invasive clones, impairing in vivo mouse colonization but increasing endothelial attachment and host mortality.

Selective targeting of cancer cells may improve therapeutic efficacy while reducing adverse effects. Here, Ueki et al.report selective activation of an anticancer drug upon removal of an acetylated lysine group by histone deacetylases and the tumour-associated protease cathepsin L.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Thrombospondin-1 (TSP-1) activates latent TGF-β in the extracellular matrix. Here the authors show that inappropriate activation of latent TGF-β in murine, bovine and human lung by monocyte-produced TSP-1 causes pulmonary hypertension, and that interference with the activation process prevents disease development.

A soluble factor induced by Plasmodiuminfection promotes hemocyte differentiation and increases mosquitoe resistance to subsequent infections. Here the authors show that this factor consists of a Lipocalin/Lipoxin A4 complex, and that insects can metabolize arachidonic acid to produce lipoxins.

Multi-omics analyses of sputum samples from patients with COPD identify host–microbe interactions as potential therapeutic targets.

Multi-omic single-cell and spatial analyses of lung cancer brain metastases from multiple cohorts identify high levels of chromosomal instability and a neural-like profile in brain metastases compared with primary tumors.

Single-cell RNA-seq reveals the cellular heterogeneity in development and disease. Here the authors present a single-nucleus RNA-seq2 that allows deep characterization of nuclei isolated from frozen archived tissues, apply it for transcriptional profiling of individual hepatocytes, and determine a functional crosstalk between liver zonation and ploidy.

Brigger et al. show that adipose tissue eosinophil dysfunction with age underpins physiological features of ageing, including global inflammation, loss of physical fitness and myeloid skewing. Eosinophils transferred from young to aged mice reversed these features and improved immunological fitness in old age, in part via IL-4.

Single-cell analysis reveals how anti-hypertensive drugs affect the risk of severe disease in patients with COVID-19 who have hypertension.

Analysis of a chromosome-level bowfin genome assembly sheds light into neopterygian fish evolution. Chromatin accessibility and gene expression profiling provides insight into bowfin embryonic development.

The developing mouse gut endoderm, mapped at single-cell resolution, reveals trajectories of cell differentiation before and during gastrulation and the emergence of regionalized cell identities along the anterior–posterior axis of the gut tube.

Proteins SBP1 and MAHRP1 of the human malaria parasite are required for sequestration of infected red blood cells in major organs. Here, De Niz et al. identify homologous proteins in the rodent parasite Plasmodium berghei, showing that they play similar roles and supporting the usefulness of malaria mouse models.

Single-cell transcriptomics reveals immune and stromal compartment remodeling, including the enrichment of unique populations of epithelial cells and CD4⁺ T cells, in asthmatic lungs

CEP63 is a centrosomal protein that is mutated in the microcephaly disease Seckel syndrome. Here the authors disrupt Cep63 in the mouse and find that neural progenitor cells undergo p53-dependent cell death, and uncover a role for CEP63 in ensuring correct meiotic recombination in male gametes.

It is becoming increasingly clear that the three-dimensional organization of chromatin within the nucleus plays a role in regulating gene expression. Here, Ito et al.demonstrate that the disruption of chromocenter clustering in mature neuronal cells results in specific transcriptional and behavioural defects in mice.

Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein, critical for proper cardiac function under stress conditions. Here the authors show that the small heat–shock protein αB-crystallin interacts with FAK and protects it from calpain-mediated proteolysis in stressed rat cardiomyocytes.

Sphingosine-1-phosphate is a bioactive lipid with various physiological roles. Here, Silva et al. show that sphingosine-1-phosphate signalling in the hypothalamic arcuate nucleus regulates food intake of rodents, and that this process is altered in animal models of obesity and cancer anorexia.

Scorpion venom causes thousands of deaths worldwide. Here the authors show that the envenomation acts via prostaglandin E2 leading to inflammasome activation and lung pathology, counterbalanced by inflammation-limiting LTB4, and that COX inhibitors or exogenous LTB4 rescue the venom-induced mortality in mice.

While heart disease, dementia and liver disease often co-occur, multi-organ imaging is needed for deeper elucidation of these cross-organ links. Here, the authors use image-derived phenotypes to describe underlying associations between heart, brain and liver health in a large population cohort.

ADAR1 is an adenosine deaminase that acts on double-stranded RNA. Orkin and colleagues show that ADAR1 protects hematopoietic stem cells from interferon-induced insult and is needed to maintain long-term hematopoiesis.

A set of ready-to-use tools for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq facilitates the implementation of single-cell technologies in clinical settings and the construction of single-cell tumor atlases.