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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.

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.

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.

Prenatal testing usually requires invasive sampling; here molecular counting of parental haplotypes in the maternal plasma allows the fetal genome to be deciphered and molecular counting of individual alleles enables the fetal exome to be captured.

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.

A microfluidic valve that amplifies the pressure in a fluid channel enables the realization of static microfluidic digital control logic. This in turn could enable more versatility and integration in the control of flows in ‘lab-on-a-chip’ systems.

New hepatitis C treatments are urgently needed. Working with a high-throughput microfluidic affinity assay for RNA-protein interactions, Quake and colleagues identify a small molecule that negatively affects HCV replication in cell culture by inhibiting the binding between the nonstructural protein 4B and the viral RNA genome.

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.

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.

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.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.

Semipermeable proteinosome membranes allow complex DNA message communication through compartmentalization and protect the DNA circuits from degradation in a biological environment.

Georgiou and colleagues discuss rapidly evolving methods for high-throughput sequencing of the antibody repertoire, and how the resulting data may be applied to answer basic and translational research questions.

Fordyce et al. measure the sequence specificity and affinity of DNA-binding proteins using an improved microfluidic device. They characterize binding of 28 yeast transcription factors, several of which had proved intractable to previous approaches.

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.

Experiments in mice show that brain circuitry centred on the posteromedial nucleus of the cortical amygdala has a key role in consolidating socially transmitted long-term memories.

Single-cell genome sequencing can provide detailed insights into the composition of single genomes that are not readily apparent when studying bulk cell populations. This Review discusses the considerable technical challenges of amplifying and interrogating genomes from single cells, emerging innovative solutions and various applications in microbiology and human disease, in particular in cancer.

Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.

The liver parenchyma consists of several cell types, but the origin of this tissue in humans is unclear. Here, the authors perform single cell RNA sequencing of human fetal and adult liver to identify a hepatobiliary hybrid progenitor population of cells, which have a similar gene signature to mouse oval cells.

Recent computational and experimental advances enable noninvasive inference of cell type in cell-free nucleic acid liquid biopsies, expanding their use across diverse settings.

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.

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.

Binding studies with systematically mutagenized RNA and RNA-binding proteins allow insight into the relationship between an RNA sequence, its structure and its function.

Spatial and single-cell transcriptomic analyses of the mouse basolateral amygdala reveal transcriptomic signatures, spatial resolution and interactions of cells that constitute the memory engram, including crucial neuron–astrocyte interactions.

The authors identify long-lasting transcriptional programmes in neurons and glia that are associated with the storage of a remote memory.

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

Single-cell transcriptomics analysis of endometrium samples from healthy women collected across the menstrual cycle provides insights into the cellular and molecular changes surrounding and during the implantation window in the absence of pregnancy.

A combination of in vitro protein synthesis and microfluidics is used to measure protein-protein interactions between 43 proteins in Streptococcus pneumoniae. The method does not require expression within cells and is amenable to large-scale experiments.

Antibodies that bind to both H1 and H3 influenza strains exist in the pre-vaccination serum repertoire of healthy adults; most vaccine-elicited clonotypes bind either H1 or H3 strains.

Einav and colleagues characterize peripheral immune blood cells from pediatric patients with severe natural dengue infections. Their findings suggest that disease progression is associated with an inflammatory phenotype accompanied by impaired interferon response, defective antigen presentation and regulation of effector lymphocyte responses.

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.

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 microfluidic mixing device for multiple, rapid and automated single-molecule measurements permits the study of macromolecule properties under varying environmental conditions. Also in this issue, Gambin et al. present another microfluidic mixing device for rapid single-molecule measurements.

Senescent cells in fat and liver are shown to attract M1-like macrophages with increased expression of the NAD-consuming enzyme CD38, leading to their local accumulation and providing a mechanism for the age-associated decline in tissue NAD⁺ levels.

Expression signatures from cell-free RNA of pregnant women can be used to reveal normal biology of pregnancy and predict development of pre-eclampsia.

The two copies of each chromosome in a diploid organism may contain different patterns of genetic variants. Fan et al. describe a microfluidic device capable of isolating each of the sister chromatids from single cells, allowing whole-genome haplotyping by sequencing and arrays.

The detrimental effects of aged blood on cognition and nervous system function in mice can be combatted by targeting brain endothelial cell dysfunction via inhibition of aberrant VCAM1 signaling at the blood–brain barrier.

The use of colloidal titanium dioxide particles as lenses enables single-molecule imaging to be performed at temperatures as high as 70 °C.

A metasurface optofluidic platform enables dynamic intensity and spectral control of light fields.

Latrophilin-3 organizes synapses through a convergent dual-pathway mechanism in which Gα_s signalling is activated and phase-separated postsynaptic protein scaffolds are recruited.