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Rare cells are often biologically and clinically important, but their low abundance makes them challenging to study using single-cell transcriptomics. Here, the authors develop PURE-seq which integrates FACS and PIP-seq to directly sequence ultra-rare cells. It captures cells at 1 in 1,000,000 rarity, which the authors demonstrate by profiling circulating tumor cells and identifying Egr1 as a regulator of mouse hematopoietic stem cell aging.

Rice paddies contribute to atmospheric methane (CH₄) levels. Here the authors show that increasing levels of the rice plant hormone PSY can reduce CH₄ emissions by over 50% via alteration of microbial H₂ cycling in the rhizosphere.

Ten people who mattered this year.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Bennett et al. conducted a population-based study in adolescents and young adults with gliomas, revealing the specific molecular alterations and identifying potential subclassifications and targets.

Using proximity-based screening, protein engineering, and structural analysis, this study describes the development of a p62-based biodegrader for the clearance of organelles and aggregated proteins by autophagy-targeted degradation.

Rigorous measurement of adaptation policies is crucial to implementing successful climate policy. Policy analysis of 41 countries shows an 87% increase in adaptation initiatives since 2010, suggesting that concrete adoption of such practices is growing.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

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).

Stress resilience is the maintenance of mental health despite adversity. Here, the authors show that how we typically evaluate adverse events is a key resilience factor and that improving it goes along with improved resilience.

A wide range of policies and actions can be used to address energy insecurity, and there are many actors and institutions to carry them out. This Perspective provides an overview of the many levers, or opportunities, that electricity sector actors have to reduce energy insecurity and affordability in the United States.

Emerging bioelectronic technologies enable real-time monitoring and precise modulation of plant physiology and environmental conditions. These technologies have the potential to accelerate basic plant science research and transform sustainable agriculture.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Capillary-associated macrophages are selectively lost over time, contributing to impaired vascular repair and reduced tissue perfusion in older mice.

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.

A trail-blazing astronomer, a climate revolutionary and a transplant pioneer are some of the people behind this year’s big stories.

Half a century after Apollo, Nature profiles five researchers who are shaking up lunar exploration.

Picks include a quantum pioneer, a co-discoverer of Ebola and a bioethicist-turned-activist.

Transition from a Fellow to an Attending can be challenging; these challenges can be amplified for women, especially at a new institution. Here are lessons I learnt that might help others with improving this transition.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Single-cell transcriptomic analyses of Plasmodium falciparum and Anopheles gambiae reveal key developmental stages, processes and factors in parasite–mosquito interactions and identify potential targets for blocking malaria transmission.

An improved, single-cell lineage-tracing system, based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility, is used to define the clonal architecture of haematopoietic stem cells.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

This Case Study describes an 18-year-old Somali man who initially presented to medical care with behavioral problems and was later diagnosed as having Klinefelter syndrome. Presented from the perspective of the primary care provider, this case illustrates the challenges in the clinical diagnosis and issues associated with long-term management of this relatively under-recognized condition.

The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

Detection of ripples in space-time kicks off new era in physics.

Ovarian cancer cells invade and metastasize into adipose tissue. By designing biomimetic organo-hydrogels, the authors reveal how the mechanical anisotropy and microstructure of adipose tissues jointly guide invasive migration.

This rapid realist review of universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools finds that interventions appear to work best when school staff are trained and the school climate is supportive. Interventions may be less effective for boys, gender minority students and bisexual students.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

It remains poorly understood how the onset of Alzheimer’s disease affects spatial cognition. Here, the authors report that spatial coding in grid cells deteriorates over time in a mouse model of Alzheimer’s disease during the early stages of pathology while place cell and head direction coding remain intact.

CD8⁺ T cell–macrophage interactions have a central role in impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia in a mouse model of long COVID.

Cikes et al. report dysregulation of glycerophosphocholine (GPC) metabolism in aged mouse muscle, which they functionally link to severe glucose intolerance. Correspondingly, muscle GPC levels are altered in both older adults and patients with type 2 diabetes.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.