Search

Yong et al. highlight how sampling conditions affect metabolic profile in renal cancer, showing that prolonged ischemic exposure disrupts tissue metabolome stability and masks important phenotypes, such as suppressed gluconeogenesis.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

A metabolomics study on the ischaemic heart identifies succinate as a metabolite that drives the production of reactive oxygen species and contributes to ischaemia-reperfusion injury; pharmacological inhibition of succinate accumulation ameliorates ischaemia-reperfusion injury in a mouse model of heart attack and a rat model of stroke.

Repair of defects in the common bile duct is hampered by a lack of healthy donor tissue. Developing human extrahepatic cholangiocyte organoids and testing them in mouse models may provide a way to overcome this limitation.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

Whole-gene sequencing of microdissected gastric glands from individuals with and without gastric cancer reveals distinct patterns of somatic mutations and provides insights into influences on the somatic evolution of the gastric epithelium.

The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

Persistent DNA lesions can occur throughout the human lifespan and can remain in the genome of affected cells for several years and generate a substantial proportion of the mutational burden.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

Epithelioids are genetically stable, self-sustaining three-dimensional cultures. They may be used to investigate various aspects of epithelial biology over several months without need for passaging. In this paper, mouse epithelioids are used to identify drivers of clonal expansion in the esophagus.

The Human Endometrial Cell Atlas integrates single-cell transcriptomic datasets from women with and without endometriosis. Novel and known cell types are registered using spatial transcriptomics to provide a comprehensive map of the human endometrium in controls and endometriosis cases.

The cellular effects of cold preservation in heart transplantation and how warm ischaemia leads to damage are unclear. Here the authors identify succinate accumulation as a major damaging metabolic change in warm ischaemia.

Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression.

The dysfunction of IL-10 secreting regulatory B cells has been linked to the pathogenesis of autoimmune disease. Here the authors show that low dose IL-2 therapy can enhance IL-10 production in regulatory B cell populations via the modulation of BACH2.

Single-cell RNA sequencing and 3D imaging have revealed the cellular changes and structural reorganization that occur during the progression of human chronic liver disease and as the liver attempts to regenerate.

Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.

Multi-omics profiling of 45 human lung samples highlights 80 different cell types along the proximal to distal axis of the lung with certain cell types showing enrichment for disease-associated genes. An immune niche for IgA-expressing plasma cells within airway submucosal glands (SMG) is also identified.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

Sequencing of individual human lymphocyte clones shows that they are highly prone to mutations, with higher burdens in memory cells than in naive cells arising from mutational processes associated with differentiation and tissue residency.

Wesley et al. describe the developmental trajectories of human foetal liver cell types at single-cell resolution and generate bipotential hepatoblast organoids, which can serve as a new platform to investigate human liver development.

Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively.

The E3 ubiquitin ligases RNF43/ZNRF3 are often mutated in cancer but their precise contribution to liver disease is unknown. Here, the authors show that RNF43/ZNRF3 alterations predispose to liver cancer by controlling the differentiation and lipid metabolic state of hepatocytes.

NanoSeq is used to detect mutations in single DNA molecules and analyses show that mutational processes that are independent of cell division are important contributors to somatic mutagenesis.

Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.

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

Genome sequencing of hundreds of normal colonic crypts from 42 individuals sheds light on mutational processes and driver mutations in normal colorectal epithelial cells.

Bioengineered biliary tissue suitable for biliary reconstruction is obtained from cholangiocyte organoids derived from human primary extra- or intrahepatic duct cholangiocytes.

A protocol for generating biliary epithelial cells from human pluripotent stem cells facilitates disease modeling and drug screening.

Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.

A single-center, observational cohort study assessing the mitochondrial bioenergetics of left ventricular tissue from patients undergoing coronary artery bypass grafting surgery suggests that viable myocardium has global alterations in bioenergetics and transcriptome without large regional differences between areas with or without inducible ischemia.

Due to the difference between rodent, porcine and human nerve morphology, Gupta et al. propose an integrative approach of computational modelling and ex vivo electrophysiology studies to identify clinically relevant optimal parameters for human peripheral nerve stimulation as a therapeutic tool. The agreement between results validate the use of computer simulations as a first step toward determining stimulation parameters to provide input criteria for device design and dose selection prior to first-in-human trials.

Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.

The gut microbiota and their proximate immune cells engage in a dialog of reciprocal regulation. James and colleagues describe how immune cell and microbiotal populations vary along the length of the human colon.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

Jarvis et al demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A)-driven acquisition of CD73 expression, which along with CD39, enables expanded Tregs to convert ATP to immunosuppressive adenosine. Given this, the data suggests that Treg expansion protocols should be optimised for CD39/CD73 co-expression to enhance therapeutic potential.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

An analysis of single-cell transcriptomics datasets from different tissues shows that ACE2 and TMPRSS2 are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of ACE2 is associated with genes involved in innate immunity.

In this Review, Petrus-Reurer et al describe the roles of both innate and adaptive immune responses in allogeneic graft rejection, in addition to discuss how such responses are determined by the cellular therapy of interest. They also describe the range of in vitro and in vivo approaches used to examine the immunogenicity of cellular therapies and consider potential confounders and strategies that can be employed to ameliorate immune rejection.