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The authors show that, in a chronic social defeat stress rodent model, a subset of male and female mice avoided social interaction with non-aggressive, same-sex juvenile mice and did not develop context-dependent social reward following these encounters.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.

Distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, calibrating the ability of the immune system to respond to physical threats.

A platform for probing the mechanics and migratory dynamics of a growing model breast cancer reveals that cells at the invasive edge are faster, softer and larger than those in the core. Eliminating the softer cells delays the transition to invasion.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

Male-pattern baldness (MPB) is related to dysregulation of androgens. Here, authors show that MPB (but not androgens) is associated with skin cancer risk, particularly in the scalp region, suggesting that sun exposure, rather than androgens, is the main driver.

Many important cellular structures in the body are curved at the scale of multiple cell lengths. Cells respond collectively to this curvature, and it influences their migration during development and growth.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

Inaccurate cell segmentation has been the major problem for cell-type identification and tissue characterization of the in situ spatially resolved transcriptomics data. Here we show a robust cell segmentation-free computational framework (SSAM), for identifying cell types and tissue domains in 2D and 3D.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

The current peripherally acting mu-opioid receptor antagonists present limited permeability and pharmacokinetic properties. Here, the authors develop a drug delivery approach based on AG10, which demonstrates the impact of mu-opioid receptors in the central nervous system in precipitating opioid-induced constipation.

Here, Imamuraet al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Analysis of data from a smartphone-based app designed for large-scale tracking of potential COVID-19 symptoms, used by over 2.5 million participants in the United Kingdom and United States, shows that loss of taste and smell sensations is predictive of potential SARS-CoV-2 infection.

Li et al. define an adaptive resistance mechanism against FGFR inhibitor treatment in breast cancer attributed to loss of BRG1 chromatin recruitment, reactivation of YAP-dependent enhancers and upregulation of amino acid-induced mTORC1 activity.

Wei Zheng and colleagues report the results of a large-scale genome-wide association study of colorectal cancer in East Asians. They identify six new susceptibility loci, including variants near TCF7L2 and TGFB1.

Myoepithelial cells prevent tumour growth and invasion in DCIS. Here, the authors show that p63 and TCF7 cooperate to regulate a transcription factor network for the maintenance of normal myoepithelial function and altered expression of these genes perturb myoepithelial function in DCIS to promote invasive progression.

Diffuse large B-cell lymphoma is an aggressive heterogeneous tumour type with poorly understood aetiology. Here, Green et al. show that transient expression of Bcl6in haematopoietic stem cells is sufficient to induce mature B-cell lymphoma, indicating that it acts as a ‘hit-and-run’ oncogene.

Flanigan et al. show that activation of inhibitory neurons in the lateral habenula by the neuropeptide orexin (hypocretin) promotes both inter-male aggression and conditioned place preference for contexts associated with winning aggressive contests.

Neuroendocrine carcinomas (NECs) arise from different anatomic sites, but have similar histological and clinical features. Here, the authors show that the epigenetic landscape of a range of NECs converges towards a common epigenetic state, while distinct subtypes occur within neuroendocrine prostate cancer contributing to intratumor heterogeneity in clinical samples.

Langseth et al. present cell type maps of human cortical tissue sections and show an efficient and robust workflow to accurately resolve anatomical organization of human brain tissue.

Multiplexed imaging of 3,660 chromosomal loci in individual mouse embryonic stem cells by DNA seqFISH+ with immunofluorescence of 17 chromatin marks and subnuclear structures reveals invariant organization of loci within individual cells, and heterogeneous and long-lived distinct combinatorial chromatin states in cellular subpopulations.

How the rainfall intensity of tropical cyclones changes with climate change is not well known. Here, the authors show that while the rain rate in the outer region of TCs is clearly increasing between 1999 and 2018, it decreases significantly in the inner-core of TCs during 1999-2018.

During embryogenesis, the cytoplasmic protein Myomarker (MYMK) mediates muscle fibre formation by fusion of myoblasts. Here, the authors identify autosomal recessive mutations in MYMK that cause Carey-Fineman-Ziter syndrome in humans, and model the disease variants in zebrafish.

Tissue-based functional genomics resources including molecular quantitative trait loci datasets lack diversity in ancestry and tissue types and thus are inadequate for comprehensively investigating gene regulation. Global efforts to increase the tissue diversity will help achieve more equitable medical care.

The molecular processes that lead to neuroendocrine prostate cancer after treating prostate adenocarcinoma (PRAD) are not well understood. Here the authors show that regulation by FOXA1 and changes in the epigenomic profile drive the transition from PRAD to a neuroendocrine phenotype.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Proliferative lupus nephritis is the most severe form of lupus nephritis. Outcomes of patients with proliferative lupus nephritis improved dramatically following the introduction of corticosteroids and cyclophosphamide, but many patients still develop end-stage renal disease. In this Review, Tesar and Hruskova discuss the clinical course of lupus nephritis, factors that predict outcomes, current induction and maintenance treatments, and recent advances in treatment options.

MIRA facilitates accurate inference of cell state trees and regulatory mechanisms driving cell fate decisions using single-cell multimodal data profiling gene expression and chromatin accessibility.

An adversarial domain translation framework is presented for scalable integration of single-cell atlases across samples, technical platforms, data modalities and species.

The mechanism underlying the dissemination of diffuse large B-cell lymphoma (DLBCL) is unclear. Here, the authors show that STAT3 controls amoeboid migration in DLBCL via the transcriptional activation of RHOH, which then releases RhoA from RhoGDIγ-mediated suppression, or via regulating microtubule dynamics to activate RhoA.