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Advances in organoid culture have enabled the modelling of many aspects of organs in vitro, transforming experimental biology. This Review provides a comprehensive overview of the current and emerging liver and pancreas organoid technologies and discusses current limitations and future directions.

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

An analysis of 18 metagenomic datasets of individuals with colorectal cancer, adenomas and healthy controls yields improved cancer prediction accuracy based solely on gut metagenomics, as well as the identification of new species associated with the development of cancer.

Our tools for understanding phase transitions at thermal equilibrium do not usually apply to granular matter. However, a vibrating quasi-one-dimensional system displays dynamic behaviour common to classic phase transitions.

Perochon et al. show in Drosophila that gut-derived reactive oxygen species and FGF induce tracheal remodelling after intestinal damage, which in turn promotes intestinal regeneration by activating intestinal stem cells.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The combination of tumor barcoding with CRISPR-mediated targeting of tumor suppressors allows quantitative analysis of tumor-suppressor function during tumor growth in vivo.

Particle-attached bacteria play a key ecosystem role by degrading complex organic materials in the ocean. Here, the authors use model marine microbial communities to show that community composition and interspecies interactions can significantly slowdown the rates of particle turnover in the environment.

Neonatal brain dynamics are not well understood. Here, the authors characterise brain transient states in neonates, and show that preterm infants display altered whole brain dynamics and an atypical repertoire of regional transient states, which are associated with behavioural outcomes at 18 months of age.

The genetic and pathogenetic basis of heart failure is incompletely understood. Here, the authors present a high-fidelity tissue collection from rapidly preserved failing and non-failing control hearts which are used for eQTL mapping and network analysis, resulting in the prioritization of PPP1R3A as a heart failure gene.

Vandenberg et al. identify differing roles of yeast DNA polymerases during accurate and mutagenic synthesis past common and rare ultraviolet light photoproducts. Similar mechanisms may contribute to driver mutations causing skin cancer in humans.

Micro-scale microbial community dynamics can substantially alter the fate of sinking particulates in the ocean thus playing a key role in setting the vertical flux of particulate carbon in the ocean.

Macrocyclic peptides are promising scaffolds for chemical tools and potential therapeutics, but their synthesis is currently difficult. Here, the authors report the characterization of Ulm16, a peptide cyclase of the penicillin-binding protein (PBP)-type class of thioesterases, that catalyzes head-to-tail macrolactamization of nonribosmal peptides of 4–6 amino acids in length.

Glucocorticoid hormones (GCs) are of critical importance for maintaining brain health, but their involvement in mental disorders is poorly understood. Here the authors show how GCs act through hippocampal mineralocorticoid and glucocorticoid receptors to impact the gene regulatory programs underpinning neuronal plasticity, ciliogenesis and behavioral adaptation.

Transplantation of healthy photoreceptor cells has been shown to rescue blindness. Here, the authors show that rather than donor cells integrating into the host retina, the predominant mechanism underlying this rescue involves exchange of cytoplasmic material between donor and host cells in vivo.

Using millimetre-scale replicate granules from an enhanced biological phosphorus removal reactor, the authors observe strain-level variability providing insights into the intrinsic drivers of microbial assembly at relevant spatial scales.

The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.

Williams et al. show that structural and functional brain asymmetry is already seen in the newborn brain, but that adult patterns of brain asymmetry are not fully developed.

In vivo screening of pro-metastatic factors in a genetically engineered mouse model of lung cancer uncovered the CD109–JAK–STAT3 axis as a key contributor of metastatic dissemination of lung cancer cells. Activation of this pathway predicts poor outcome in patients with cancer, and its pharmacological inhibition dramatically reduces the metastatic ability of tumor cells, suggesting that it might be an effective intervention in patients.

In vivo analysis of pairwise combinations of tumor suppressor losses using a barcode-based assay in mice identifies unpredicted genetic interactions and shows that the effects of tumor suppressor alterations can be context-dependent.

T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

The boundary between West and East Antarctica is a tectonic feature that bisects the Ross Ice Shelf. This boundary constrains ocean circulation under the ice, which affects ice stability, according to airborne survey data and ocean simulations.

The combination of cellular barcoding and treatment with a library of small molecules before injecting the treated cells into mice allows the screening for compounds that inhibit metastatic seeding.

Soil-mimicking microfluidic devices were developed to visualise and characterise the swimming behavior of soil bacteria B. diazoefficiens. Molity parameters, obtained with high statistical accuracy, enable simulations of their motion in real soils.

The mTORC1 complex has been implicated in tumorigenesis owing partially to its ability to increase protein translation; now, mTORC1 activity in the mouse intestine is shown not to be required for normal homeostasis but to be necessary for the triggering of tumorigenesis by APC mutations, suggesting that it could be a good target for the prevention of colorectal cancer in high-risk patients.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements.

In a mouse model of small-cell lung cancer and in human tumours, activation of the Notch pathway can lead to a cell fate switch of neuroendocrine cells to less proliferative non-neuroendocrine cells, generating intratumoural heterogeneity.