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A ‘mouse atlas’, comprising single-cell transcriptomic data from more than 100,000 cells from 20 organs and tissues, has been created as a resource for cell biology.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

Epigenetic causes of intra-tumoural heterogeneity are crucial in paediatric cancers with low mutation rates, such as hepatoblastoma. Here, the authors characterise transcriptional heterogeneity in hepatoblastoma using histology-guided RNA sequencing and functional studies in patient-derived tumoroids, and find how the embryonic biliary lineage program, Wnt, and paracrine signalling can promote tumour proliferation.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

In this work, authors assess airway microbiome dynamics to show bacterial pneumonia in critically ill COVID-19 patients is significantly associated with death, corticosteroid treatment, disruption of the lung microbiome and a distinct pulmonary host response.

Characterization of tumour and tumour microenvironment by single-nucleus RNA sequencing reveals that the murine GL261-GSC glioblastoma model recapitulates the features of TME^Med glioblastoma, the most common subtype of human glioblastoma.

There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.

The difference between children and adults in response to SARS-CoV-2 infection is not clearly established. Here the authors use gene expression analysis of nasopharyngeal samples from children and adults and show a higher level of immune response in children compared to adults, including of B and T cell activation.

DiMeLo-seq uses native long-read sequencing to examine protein–DNA interactions by mapping exogenous methylation marks generated by a nonspecific DNA methyltransferase, as well as profile endogenous CpG methylation simultaneously.

Pushkarev et al. present the first human genome sequence obtained using single-molecule sequencing technology. These results demonstrate that human genome sequencing—previously the turf of large sequencing centers—is now within reach of an individual lab in a matter of weeks.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

A study identifies the AT1 cell as a cell of origin for lung adenocarcinoma, and demonstrates that expression of oncogenic KRAS in differentiated AT1 cells reprograms them back into AT2 stem cells that generate indolent lepidic tumours.

An atlas of noncoding RNA in aging and rejuvenated mice identifies a set of deregulated miRNAs.

An analysis of skeletal stem cells in mice reveals that bone ageing occurs at the level of local niches affecting skeletal and haematopoietic lineage output, which may influence systemic aspects of multi-organ physiological ageing.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

Human induced pluripotent stem cell derived cardiomyocytes are a powerful model for cardiogenesis and disease in vitro. Here the authors comprehensively map cardiac differentiation using multiple modalities, including single-cell RNA seq and CyTOF, in cells with a gain  or loss of function in key cardiac transcription factors.

Expression profiling on 75,000 single cells creates a comprehensive cell atlas of the human lung that includes 41 out of 45 previously known cell types and 14 new ones.

Not all cells in a tumor are alike, but our ability to characterize cancer heterogeneity in detail has been limited. Dalerba et al. use high-throughput single-cell expression analysis to define clinically relevant subpopulations in normal and cancerous colon tissue.

Since 1987, immortalized cells from the ovary of a Chinese hamster have been the workhorse for producing recombinant therapeutics, including monoclonal antibodies, blood factors, hormones, growth factors and enzymes. Xu et al. provide the genome sequence of the ancestral CHO-K1 cell line, which should aid in the optimization of current production cell lines.

Analyses of circulating cell-free RNA (cfRNA) in blood samples from pregnant mothers identify changes in gene expression that could be used in liquid biopsy tests to identify and monitor individuals who are at risk of preeclampsia.

Heterogeneity within populations of stem cells, cancer cells or other cell types of interest presents a formidable barrier to analysis. Lu et al. use viral barcoding and high-throughput sequencing to track the differentiation of single hematopoietic stem cells in vivo.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

A single-cell transcriptomic atlas across the lifespan of the mouse, denoted Tabula Muris Senis, provides molecular information about the hallmarks of ageing in a range of tissues and cell types.

Leng et al. uncover the molecular signature of neuronal subpopulations that are selectively vulnerable to tau aggregation and death early in Alzheimer’s disease in the human entorhinal cortex and other brain regions, validating RORB as a marker.

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

The identification of a complex haematopoietic system in a colonial tunicate sheds light on the evolution of the mammalian blood system.

The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

A systematic evaluation of various single-cell RNA-seq approaches reports their sensitivity, accuracy and reproducibility and establishes the high performance of a high-throughput microfluidic method.

Single-cell transcriptome analysis enables the direct measurement of cell types and lineage hierarchies of the developing distal lung epithelium and identifies a population of bipotential alveolar progenitor cells.

The authors present a FACS-based protocol for the purification of human skeletal stem cell lineages from a variety of tissue sources, alongside in vitro and in vivo skeletogenic functional assays, human xenograft mouse models and single-cell RNA sequencing analysis.

Cell types affected by various diseases are inferred from cell-free RNA.