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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Poor access to suitable light-sheet microscopes remains a big obstacle for many end-users in biomedical research. Here, the authors present descSPIM, a low-cost, low-expertise light-sheet microscope for routine 3D imaging of cleared samples.

The prediction of mortality due to prostate cancer remains challenging. Here, the authors perform trans-ancestry metaanalysis with a focus on binding sites of the androgen receptor and develop a polygenic risk score.

Genome-wide association and fine-mapping analyses in approximately 260,000 Japanese individuals combined with a newly constructed Japanese-specific genotype reference panel identify hundreds of new loci and putative causal variants for 63 quantitative traits.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

The fetal murine foregut develops into visceral organs via interactions between the mesoderm and endoderm, but how is unclear. Here, the authors use single cell RNAseq to show a diversity in organ specific splanchnic mesoderm cell-types, infer a signalling network governing organogenesis and use this to differentiate human pluripotent stem cells.

Surface-enhanced Raman spectroscopy (SERS) visualizes fingerprints of intermolecular vibrations of many metabolites. Here the authors report a SERS imaging technique that enables the visualization of metabolites distribution and automated extraction of tumour boundaries in frozen tissues.

A light-harvesting chlorophyll-binding protein complex from an Antarctic green alga called Prasiola crispa can excite photosystem II with low energy far-red light. Here, through Cryo-EM analysis, the authors reveal its ring-shaped structure with 11-fold symmetry at 3.13 Å resolution.

The treatment of ROS1-rearranged non-small cell lung cancer with the TKI crizotinib is limited due to the emergence of resistance. Here, the authors develop a new ROS1/NTRK inhibitor, DS-6051b, which overcomes crizotinib resistance in preclinical models.

The circadian transcription factors BMAL1:CLOCK bind to E/E′-boxes in gene regulatory elements of their targets and facilitate rhythmic expression. Here, the authors mutate the Per2 promoter E’′-box in mice and observe that cell- and tissue-autonomous oscillations are dampened and that animals are less susceptible to jet lag.

Genome-wide analyses in BioBank Japan and populations of European ancestry identify new risk loci for atrial fibrillation. A polygenic risk score constructed from the cross-ancestry meta-analysis is associated with increased risk of long-term cardiovascular mortality.

Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here, the authors show in a mice model that insulin action in the gut may play a protective role in the development of NASH and HCC in diabetes.

Here, the authors identify six risk SNPs for systemic sclerosis by performing GWAS on Japanese patients and meta-analyzing Japanese and European GWAS datasets. Downstream analyses indicate that B cells contribute to pathogenesis.

The Fanconi anemia pathway is involved in the signaling of DNA damage. Several Fanconi anemia proteins have been identified, but how the pathway is actually activated was unclear. Now, work on chicken DT40 cells indicates that phosphorylation of FANCI at multiple sites triggers FANCD2 monoubiquitination and DNA-damage repair.

Vascularized, functional human liver is generated from human induced pluripotent stem cells (iPSCs) by transplantation of liver buds created in vitro (iPSC-LBs); hepatic cells self-organized into three-dimensional iPSC-LBs, and human vasculatures in iPSC-LB transplants became functional by connecting to host vessels, stimulating maturation of iPSC-LBs into tissue resembling adult liver and performing liver-specific functions.

This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.

Signaling via the cytokine IL-9 receptor regulates humoral recall responses. Kitamura and colleagues report that IL-9 triggers memory B cells to proliferate and terminally differentiate into antibody-secreting cells rather than re-entering germinal centers.

Isolation during critical periods of development prevents development of normal social behaviours in mice, and this is thought to involve the prefrontal cortex. Here, the authors identify an activation pattern in parvalbumin-positive interneurons in the dorsal medial prefrontal cortex that when activated promotes sociability behaviours in mice.

High-speed and high-sensitive three-dimensional immunohistochemistry by using peroxidase-fused nanobodies and a tyramide signal amplification system, Fluorochromized Tyramide-Glucose Oxidase.

Frontal top-down cortical neurons implement top-down attentional control of sensory regions. The authors reveal adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are functionally integrated into local excitatory circuitry.

Cell fusion is involved in many different cellular processes including the fusion of trophoblast cells in the placenta. Matsuuraet al. identify a role for the β-catenin signalling pathway in the regulation of the transcription factor GCM1 and therefore the fusion of syncytiotrophoblast cells.

Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild infectious disease that can, however, occasionally lead to severe neurological impairments. These two studies, by Nishimura et al. and Yamayoshi et al., independently identify two different receptors for EV71—P-selectin glycoprotein ligand-1 ((PSGL-1) and scavenger receptor class B, member 2 (SCARB2) (pages 728–729) and (pages 798–801).

Stem growth in rice is regulated by an accelerator gene and a decelerator gene in parallel with gibberellic acid, and the opposite selection of these genes has led to adaptations to different environments.

Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML) is characterized by abnormal platelet function and a high risk of haematological malignancies. Here, the authors report frequent CDC25Cmutations in FPD/AML patients and suggest that this gene may influence malignant transformation in FPD/AML.

Individuals with hemophilia A lack the coagulation factor FVIII and are treated with frequent intravenous injections of FVIII agents. However, many individuals develop antibodies to FVIII and can no longer be treated by FVIII injection. Takehisa Kitazawa and his colleagues report the development of a bispecific antibody to FIXa and FX that mimics the function of FVIII. This antibody reduces bleeding in a nonhuman primate model of hemophilia A, is resistant to the inhibitory effects of FVIII-specific antibodies and has a long half-life after subcutaneous injection.

Juxtaposition of region-specific gut spheroids derived from human pluripotent stem cells in the absence of extrinsic factors results in development of segregated hepato-biliary-pancreatic anlages that recapitulate early morphogenetic events.

Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in RHOA in diffuse-type gastric carcinomas.

Takebe et al. describe a protocol for the continuous patterning of hepatic, biliary and pancreatic structures from a 3D culture of human pluripotent stem cells.