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Chen, Zhou, Xue et al. show that psychological stress leads to noradrenaline release and Alkbh5 downregulation, causing the transfer of extracellular vesicles containing m⁶A-modified RNAs to neurons to regulate innervation and pancreatic cancer development.

Using super-resolution imaging to directly observe the three-dimensional organization of Drosophila chromatin at a scale spanning sizes from individual genes to entire gene regulatory domains, the authors find that transcriptionally active, inactive and Polycomb-repressed chromatin states each have a distinct spatial organisation.

A nucleosome-spacing mechanism for human ATP-dependent chromatin assembly and remodelling factor (ACF).

A comprehensive cell atlas of the whole mouse brain with high molecular and spatial resolution is generated.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

The mechanism driving inflammatory-to-proliferative state transition during wound healing remains unclear. Here, the authors discover that SNHG26 interacts with ILF2, redirecting it from inflammatory genomic loci to the LAMB3 locus, thereby promoting wound healing.

This Review describes how single-virus tracking can be used to monitor the journey that viruses make through cells in exquisite detail. With specific examples of the entry, cellular transport and exit of selected viruses, the technicalities and benefits of this approach are revealed.

The molecular mechanisms underlying the late-onset adverse effects of radiotherapy remain to be explored. Here, the authors observe compromised wound healing capacity in irradiated skin from breast cancer survivors and highlight THBS1 as a key epigenetically primed wound repair-related gene.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

To mark the 15th anniversary of Nature Methods, we asked scientists from across diverse fields of basic biology research for their views on the most exciting and essential methodological challenges that their communities are poised to tackle in the near future.

Fatigue-resistant, photoswitchable fluorescent proteins facilitate sub-diffraction-limit imaging of living cells with low light intensity.

Imaging studies revealed that m⁶A-binding YTHDF proteins promoted phase separation of core proteins of stress granules by reducing the critical size and activation energy barrier, thus promoting the formation of stress granules in cells.

Coordination between subunits is crucial for the proper functioning of multi-component molecular machines. A single-molecule study now allows glimpses into the mechanism used by subunits of one such machine.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

The nori producing seaweed Pyropia yezoensis has heteromorphic generations that occupy distinct habitats. Here, via genome assembly, transcriptome analysis, and 13 C isotope labeling, the authors show the interplay between inorganic carbon availability and life cycle evolution in the intertidal environment.

Reverse transcriptase is an essential enzyme for HIV replication. Single-molecule studies reveal for the first time the structural dynamics of the reverse transcription initiation complex in real time. Reverse transcriptase can bind its tRNA–vRNA substrate in two opposite orientations and flip between these two states.

By exploiting a self-bending point spread function based on Airy beams, a three-dimensional super-resolution fluorescence imaging is realized. A three-dimensional localization precision in the range 10–15 nm was obtained at an imaging depth of 3 µm from ∼2,000 photons per localization.

The use of dual-objective detection with astigmatism-based three-dimensional stochastic optical reconstruction microscopy (STORM) imaging improves resolution more than twofold and removes noise in resulting super-resolution images. This allowed detailed fluorescence imaging of distinctive features of the three-dimensional actin cytoskeleton ultrastructure with single-filament resolution in cells.

In neurons the membrane-associated periodic skeleton (MPS) consists of actin, spectrin, and associated molecules. Here the authors use proteomic analysis and super-resolution imaging to provide insight into the molecular composition and organization of the MPS, and its functions in axon-diameter regulation and neurite-neurite interactions.

As part of the BICCN consortium, the authors used a single-cell transcriptomic imaging method to produce a highly defined atlas of cell types across the mouse primary motor cortex.

The ATP-dependent chromatin assembly factor (ACF) generates regularly spaced nucleosomes, but the mechanism by which ACF mobilizes nucleosomes remains poorly understood. Here, single-molecule FRET is used to monitor the remodelling of individual nucleosomes by ACF in real time; the study reveals previously unknown remodelling intermediates and dynamics, and indicates that ACF is a highly processive and bidirectional nucleosome translocase.

Polycomb Group (PcG) proteins regulate gene expression and genome architecture. Using super-resolution microscopy and molecular simulations, Waniet al. describe the organization of PcG proteins into hundreds of nano-scale protein clusters and suggest these clusters shape genome architecture.

HIV-1 reverse transcriptase (RT) is an important drug target. RT has two activities, DNA synthesis, and cleavage of a DNA–RNA hybrid. These activities require that RT bind to both DNA and RNA. Single-molecule technology is used to show that the enzyme binds to RNA and DNA in different orientations, and provide insight into how it can flip between these orientations and activities without dissociating from the substrate.

Extension of multicolor three-dimensional stochastic optical reconstruction microscopy (STORM) allows super-resolution fluorescence imaging of whole cells and quantitative characterization of subcellular structures and their spatial relationships. This was demonstrated by imaging the entire mitochondrial and tubulin networks in cells.

Chromatin remodelling enzymes (remodellers) regulate DNA accessibility of eukaryotic genomes, which rely in large part on an ability to reposition nucleosomes. Here the authors use three-colour single-molecule FRET to simultaneously monitor remodeller-induced DNA movements on both sides of the nucleosome in real-time.

Multicolour, three-dimensional stochastic optical reconstruction microscopy now makes it possible to image cellular structures with near molecular-scale resolution.

A newly identified population of neurons in the ventral medial preoptic area of the hypothalamus regulate stereotypical symptoms of illness, including fever and appetite suppression.

Tangram is a versatile tool for aligning single-cell and single-nucleus RNA-seq data to spatially resolved transcriptomics data using deep learning.

The insulation potency of CTCF depends on the number of binding sites in tandem and on upstream flanking sequences. Insulators form local chromatin ___domain boundaries and weaken enhancer–promoter contacts.

Judicious choice of probes and imaging conditions allows two-dimensional super-resolution imaging of live cells at speeds up to 2 Hz with ~25-nm resolution and three-dimensional super-resolution imaging at ~1 Hz with ~30 nm x-y and ~50 nm z dimension resolution using stochastic optical reconstruction microscopy (STORM).

The Human Cell Atlas (HCA) aims to characterize cells from diverse individuals across the globe to better understand human biology. Here, the authors lay out principles and action items that have been adopted to affirm HCA’s commitment to equity so that the atlas is beneficial to all of humanity.

The spatial organization of the genome within the nucleus impacts many processes. Here the authors combine oligo-based DNA FISH with single-molecule super-resolution microscopy to image single-copy genomic regions and, taking advantage of SNPs, distinguish allelic regions of homologous chromosomes.

The ISWI chromatin remodelers interact with extranucleosomal DNA to mediate nucleosome positioning. A new study now shows that the conserved SLIDE ___domain in the Isw2 subunit, which binds linker DNA, facilitates unidirectional linker DNA movement into nucleosomes. These findings suggest that the SLIDE ___domain functions in conjunction with the ATPase ___domain to mobilize nucleosomes.

Here, the helix–loop–helix transcription factor Ascl2 is shown to be critically important for the initiation of follicular T-helper-cell development and the germinal centre response.

Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.

ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.

'Spaghetti monster' fluorescent proteins combine the power of conventional fluorescent proteins with the benefits of commonly used epitopes. These probes are demonstrated to be extremely versatile in diverse imaging applications.

The authors generated a cell census of mouse nucleus accumbens using single-cell RNA sequencing and multiplexed error-robust FISH. These data suggest that transcriptional and spatial diversity of neuron subtypes underlies nucleus accumbens anatomic and functional heterogeneity.