Multimodal charting of molecular and functional cell states via in situ electro-sequencing.

Paired mapping of single-cell gene expression and electrophysiology is essential to understand gene-to-function relationships in electrogenic tissues. Here, we developed in situ electro-sequencing (electro-seq) that combines flexible bioelectronics with in situ RNA sequencing to stably map millisecond-timescale electrical activity and profile single-cell gene expression from the same cells across intact biological networks, including cardiac and neural patches. When applied to human-induced pluripotent stem-cell-derived cardiomyocyte patches, in situ electro-seq enabled multimodal in situ analysis of cardiomyocyte electrophysiology and gene expression at the cellular level, jointly defining cell states and developmental trajectories. Using machine-learning-based cross-modal analysis, in situ electro-seq identified gene-to-electrophysiology relationships throughout cardiomyocyte development and accurately reconstructed the evolution of gene expression profiles based on long-term stable electrical measurements. In situ electro-seq could be applicable to create spatiotemporal multimodal maps in electrogenic tissues, potentiating the discovery of cell types and gene programs responsible for electrophysiological function and dysfunction.

Self-oscillating polymeric refrigerator with high energy efficiency.

Electrocaloric1,2 and electrostrictive3,4 effects concurrently exist in dielectric materials. Combining these two effects could achieve the lightweight, compact localized thermal management that is promised by electrocaloric refrigeration5. Despite a handful of numerical models and schematic presentations6,7, current electrocaloric refrigerators still rely on external accessories to drive the working bodies8-10 and hence result in a low device-level cooling power density and coefficient of performance (COP). Here we report an electrocaloric thin-film device that uses the electro-thermomechanical synergy provided by polymeric ferroelectrics. Under one-time a.c. electric stimulation, the device is thermally and mechanically cycled by the working body itself, resulting in an external-driver-free, self-cycling, soft refrigerator. The prototype offers a directly measured cooling power density of 6.5 W g-1 and a peak COP exceeding 58 under a zero temperature span. Being merely a 30-µm-thick polymer film, the device achieved a COP close to 24 under a 4 K temperature span in an open ambient environment (32% thermodynamic efficiency). Compared with passive cooling, the thin-film refrigerator could immediately induce an additional 17.5 K temperature drop against an electronic chip. The soft, polymeric refrigerator can sense, actuate and pump heat to provide automatic localized thermal management.

Genome editing of a rice CDP-DAG synthase confers multipathogen resistance.

The discovery and application of genome editing introduced a new era of plant breeding by giving researchers efficient tools for the precise engineering of crop genomes1. Here we demonstrate the power of genome editing for engineering broad-spectrum disease resistance in rice (Oryza sativa). We first isolated a lesion mimic mutant (LMM) from a mutagenized rice population. We then demonstrated that a 29-base-pair deletion in a gene we named RESISTANCE TO BLAST1 (RBL1) caused broad-spectrum disease resistance and showed that this mutation caused an approximately 20-fold reduction in yield. RBL1 encodes a cytidine diphosphate diacylglycerol synthase that is required for phospholipid biosynthesis2. Mutation of RBL1 results in reduced levels of phosphatidylinositol and its derivative phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In rice, PtdIns(4,5)P2 is enriched in cellular structures that are specifically associated with effector secretion and fungal infection, suggesting that it has a role as a disease-susceptibility factor3. By using targeted genome editing, we obtained an allele of RBL1, named RBL1Δ12, which confers broad-spectrum disease resistance but does not decrease yield in a model rice variety, as assessed in small-scale field trials. Our study has demonstrated the benefits of editing an LMM gene, a strategy relevant to diverse LMM genes and crops.

Galeaspid anatomy and the origin of vertebrate paired appendages.

Paired fins are a major innovation1,2 that evolved in the jawed vertebrate lineage after divergence from living jawless vertebrates3. Extinct jawless armoured stem gnathostomes show a diversity of paired body-wall extensions, ranging from skeletal processes to simple flaps4. By contrast, osteostracans (a sister group to jawed vertebrates) are interpreted to have the first true paired appendages in a pectoral position, with pelvic appendages evolving later in association with jaws5. Here we show, on the basis of articulated remains of Tujiaaspis vividus from the Silurian period of China, that galeaspids (a sister group to both osteostracans and jawed vertebrates) possessed three unpaired dorsal fins, an approximately symmetrical hypochordal tail and a pair of continuous, branchial-to-caudal ventrolateral fins. The ventrolateral fins are similar to paired fin flaps in other stem gnathostomes, and specifically to the ventrolateral ridges of cephalaspid osteostracans that also possess differentiated pectoral fins. The ventrolateral fins are compatible with aspects of the fin-fold hypothesis for the origin of vertebrate paired appendages6-10. Galeaspids have a precursor condition to osteostracans and jawed vertebrates in which paired fins arose initially as continuous pectoral-pelvic lateral fins that our computed fluid-dynamics experiments show passively generated lift. Only later in the stem lineage to osteostracans and jawed vertebrates did pectoral fins differentiate anteriorly. This later differentiation was followed by restriction of the remaining field of fin competence to a pelvic position, facilitating active propulsion and steering.

The oldest gnathostome teeth.

Mandibular teeth and dentitions are features of jawed vertebrates that were first acquired by the Palaeozoic ancestors1-3 of living chondrichthyans and osteichthyans. The fossil record currently points to the latter part of the Silurian period4-7 (around 425 million years ago) as a minimum date for the appearance of gnathostome teeth and to the evolution of growth and replacement mechanisms of mandibular dentitions in the subsequent Devonian period2,8-10. Here we provide, to our knowledge, the earliest direct evidence for jawed vertebrates by describing Qianodus duplicis, a new genus and species of an early Silurian gnathostome based on isolated tooth whorls from Guizhou province, China. The whorls possess non-shedding teeth arranged in a pair of rows that demonstrate a number of features found in modern gnathostome groups. These include lingual addition of teeth in offset rows and maintenance of this patterning throughout whorl development. Our data extend the record of toothed gnathostomes by 14 million years from the late Silurian into the early Silurian (around 439 million years ago) and are important for documenting the initial diversification of vertebrates. Our analyses add to mounting fossil evidence that supports an earlier emergence of jawed vertebrates as part of the Great Ordovician Biodiversification Event (approximately 485-445 million years ago).

Spiny chondrichthyan from the lower Silurian of South China.

Modern representatives of chondrichthyans (cartilaginous fishes) and osteichthyans (bony fishes and tetrapods) have contrasting skeletal anatomies and developmental trajectories1-4 that underscore the distant evolutionary split5-7 of the two clades. Recent work on upper Silurian and Devonian jawed vertebrates7-10 has revealed similar skeletal conditions that blur the conventional distinctions between osteichthyans, chondrichthyans and their jawed gnathostome ancestors. Here we describe the remains (dermal plates, scales and fin spines) of a chondrichthyan, Fanjingshania renovata gen. et sp. nov., from the lower Silurian of China that pre-date the earliest articulated fossils of jawed vertebrates10-12. Fanjingshania possesses dermal shoulder girdle plates and a complement of fin spines that have a striking anatomical similarity to those recorded in a subset of stem chondrichthyans5,7,13 (climatiid 'acanthodians'14). Uniquely among chondrichthyans, however, it demonstrates osteichthyan-like resorptive shedding of scale odontodes (dermal teeth) and an absence of odontogenic tissues in its spines. Our results identify independent acquisition of these conditions in the chondrichthyan stem group, adding Fanjingshania to an increasing number of taxa7,15 nested within conventionally defined acanthodians16. The discovery of Fanjingshania provides the strongest support yet for a proposed7 early Silurian radiation of jawed vertebrates before their widespread appearance5 in the fossil record in the Lower Devonian series.

The oldest complete jawed vertebrates from the early Silurian of China.

Molecular studies suggest that the origin of jawed vertebrates was no later than the Late Ordovician period (around 450 million years ago (Ma))1,2. Together with disarticulated micro-remains of putative chondrichthyans from the Ordovician and early Silurian period3-8, these analyses suggest an evolutionary proliferation of jawed vertebrates before, and immediately after, the end-Ordovician mass extinction. However, until now, the earliest complete fossils of jawed fishes for which a detailed reconstruction of their morphology was possible came from late Silurian assemblages (about 425 Ma)9-13. The dearth of articulated, whole-body fossils from before the late Silurian has long rendered the earliest history of jawed vertebrates obscure. Here we report a newly discovered Konservat-Lagerstätte, which is marked by the presence of diverse, well-preserved jawed fishes with complete bodies, from the early Silurian (Telychian age, around 436 Ma) of Chongqing, South China. The dominant species, a 'placoderm' or jawed stem gnathostome, which we name Xiushanosteus mirabilis gen. et sp. nov., combines characters from major placoderm subgroups14-17 and foreshadows the transformation of the skull roof pattern from the placoderm to the osteichthyan condition10. The chondrichthyan Shenacanthus vermiformis gen. et sp. nov. exhibits extensive thoracic armour plates that were previously unknown in this lineage, and include a large median dorsal plate as in placoderms14-16, combined with a conventional chondrichthyan bauplan18,19. Together, these species reveal a previously unseen diversification of jawed vertebrates in the early Silurian, and provide detailed insights into the whole-body morphology of the jawed vertebrates of this period.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Chemical-tag-based semi-annotated metabolomics facilitates gene identification and specialized metabolic pathway elucidation in wheat.

The importance of metabolite modification and species-specific metabolic pathways has long been recognized. However, linking the chemical structure of metabolites to gene function in order to explore the genetic and biochemical basis of metabolism has not yet been reported in wheat (Triticum aestivum). Here, we profiled metabolic fragment enrichment in wheat leaves and consequently applied chemical-tag-based semi-annotated metabolomics in a genome-wide association study in accessions of wheat. The studies revealed that all 1,483 quantified metabolites have at least one known functional group whose modification is tailored in an enzyme-catalyzed manner and eventually allows efficient candidate gene mining. A Triticeae crop-specific flavonoid pathway and its underlying metabolic gene cluster were elucidated in further functional studies. Additionally, upon overexpressing the major effect gene of the cluster TraesCS2B01G460000 (TaOMT24), the pathway was reconstructed in rice (Oryza sativa), which lacks this pathway. The reported workflow represents an efficient and unbiased approach for gene mining using forward genetics in hexaploid wheat. The resultant candidate gene list contains vast molecular resources for decoding the genetic architecture of complex traits and identifying valuable breeding targets and will ultimately aid in achieving wheat crop improvement.

High-entropy polymer produces a giant electrocaloric effect at low fields.

More than a decade of research on the electrocaloric (EC) effect has resulted in EC materials and EC multilayer chips that satisfy a minimum EC temperature change of 5 K required for caloric heat pumps1-3. However, these EC temperature changes are generated through the application of high electric fields4-8 (close to their dielectric breakdown strengths), which result in rapid degradation and fatigue of EC performance. Here we report a class of EC polymer that exhibits an EC entropy change of 37.5 J kg-1 K-1 and a temperature change of 7.5 K under 50 MV m-1, a 275% enhancement over the state-of-the-art EC polymers under the same field strength. We show that converting a small number of the chlorofluoroethylene groups in poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) terpolymer into covalent double bonds markedly increases the number of the polar entities and enhances the polar-nonpolar interfacial areas of the polymer. The polar phases in the polymer adopt a loosely correlated, high-entropy state with a low energy barrier for electric-field-induced switching. The polymer maintains performance for more than one million cycles at the low fields necessary for practical EC cooling applications, suggesting that this strategy may yield materials suitable for use in caloric heat pumps.

Real-time tracking of electron transfer at catalytically active interfaces in lithium-ion batteries.

Transition metals and related compounds are known to exhibit high catalytic activities in various electrochemical reactions thanks to their intriguing electronic structures. What is lesser known is their unique role in storing and transferring electrons in battery electrodes which undergo additional solid-state conversion reactions and exhibit substantially large extra capacities. Here, a full dynamic picture depicting the generation and evolution of electrochemical interfaces in the presence of metallic nanoparticles is revealed in a model CoCO3/Li battery via an in situ magnetometry technique. Beyond the conventional reduction to a Li2CO3/Co mixture under battery operation, further decomposition of Li2CO3 is realized by releasing interfacially stored electrons from its adjacent Co nanoparticles, whose subtle variation in the electronic structure during this charge transfer process has been monitored in real time. The findings in this work may not only inspire future development of advanced electrode materials for next-generation energy storage devices but also open up opportunities in achieving in situ monitoring of important electrocatalytic processes in many energy conversion and storage systems.

Intrinsic-strain-induced ferroelectric order and ultrafine nanodomains in SrTiO3.

Nano ferroelectrics holds the potential application promise in information storage, electro-mechanical transformation, and novel catalysts but encounters a huge challenge of size limitation and manufacture complexity on the creation of long-range ferroelectric ordering. Herein, as an incipient ferroelectric, nanosized SrTiO3 was indued with polarized ordering at room temperature from the nonpolar cubic structure, driven by the intrinsic three-dimensional (3D) tensile strain. The ferroelectric behavior can be confirmed by piezoelectric force microscopy and the ferroelectric TO1 soft mode was verified with the temperature stability to 500 K. Its structural origin comes from the off-center shift of Ti atom to oxygen octahedron and forms the ultrafine head-to-tail connected 90° nanodomains about 2 to 3 nm, resulting in an overall spontaneous polarization toward the short edges of nanoparticles. According to the density functional theory calculations and phase-field simulations, the 3D strain-related dipole displacement transformed from [001] to [111] and segmentation effect on the ferroelectric domain were further proved. The topological ferroelectric order induced by intrinsic 3D tensile strain shows a unique approach to get over the nanosized limitation in nanodevices and construct the strong strain-polarization coupling, paving the way for the design of high-performance and free-assembled ferroelectric devices.

Enhancer variants on chromosome 2p14 regulating SPRED2 and ACTR2 act as a signal amplifier to protect against rheumatoid arthritis.

Genome-wide association studies (GWASs) have repeatedly reported multiple non-coding single-nucleotide polymorphisms (SNPs) at 2p14 associated with rheumatoid arthritis (RA), but their functional roles in the pathological mechanisms of RA remain to be explored. In this study, we integrated a series of bioinformatics and functional experiments and identified three intronic RA SNPs (rs1876518, rs268131, and rs2576923) within active enhancers that can regulate the expression of SPRED2 directly. At the same time, SPRED2 and ACTR2 influence each other as a positive feedback signal amplifier to strengthen the protective role in RA by inhibiting the migration and invasion of rheumatoid fibroblast-like synoviocytes (FLSs). In particular, the transcription factor CEBPB preferentially binds to the rs1876518-T allele to increase the expression of SPRED2 in FLSs. Our findings decipher the molecular mechanisms behind the GWAS signals at 2p14 for RA and emphasize SPRED2 as a potential candidate gene for RA, providing a potential target and direction for precise treatment of RA.

Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape.

Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap-a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed 'kinetic gene clusters' whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia.

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT. The heightened bacterial burdens in Bhlhe40-/- mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-γ, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in Bhlhe40-/- mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in Bhlhe40-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-γ production by Th1 cells. Altogether, we identified Bhlhe40 as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against Chlamydia.

H2O2-dependent oxidation of the transcription factor GmNTL1 promotes salt tolerance in soybean.

Reactive oxygen species (ROS) play an essential role in plant growth and responses to environmental stresses. Plant cells sense and transduce ROS signaling directly via hydrogen peroxide (H2O2)-mediated posttranslational modifications (PTMs) on protein cysteine residues. Here, we show that the H2O2-mediated cysteine oxidation of NAC WITH TRANS-MEMBRANE MOTIF1-LIKE 1 (GmNTL1) in soybean (Glycine max) during salt stress promotes its release from the endoplasmic reticulum (ER) membrane and translocation to the nucleus. We further show that an oxidative posttranslational modification on GmNTL1 residue Cys-247 steers downstream amplification of ROS production by binding to and activating the promoters of RESPIRATORY BURST OXIDASE HOMOLOG B (GmRbohB) genes, thereby creating a feed-forward loop to fine-tune GmNTL1 activity. In addition, oxidation of GmNTL1 Cys-247 directly promotes the expression of CATION H+ EXCHANGER 1 (GmCHX1)/SALT TOLERANCE-ASSOCIATED GENE ON CHROMOSOME 3 (GmSALT3) and Na+/H+ Antiporter 1 (GmNHX1). Accordingly, transgenic overexpression of GmNTL1 in soybean increases the H2O2 levels and K+/Na+ ratio in the cell, promotes salt tolerance, and increases yield under salt stress, while an RNA interference-mediated knockdown of GmNTL1 elicits the opposite effects. Our results reveal that the salt-induced oxidation of GmNTL1 promotes its relocation and transcriptional activity through an H2O2-mediated posttranslational modification on cysteine that improves resilience of soybean against salt stress.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

CellCommuNet: an atlas of cell-cell communication networks from single-cell RNA sequencing of human and mouse tissues in normal and disease states.

Cell-cell communication, as a basic feature of multicellular organisms, is crucial for maintaining the biological functions and microenvironmental homeostasis of cells, organs, and whole organisms. Alterations in cell-cell communication contribute to many diseases, including cancers. Single-cell RNA sequencing (scRNA-seq) provides a powerful method for studying cell-cell communication by enabling the analysis of ligand-receptor interactions. Here, we introduce CellCommuNet (http://www.inbirg.com/cellcommunet/), a comprehensive data resource for exploring cell-cell communication networks in scRNA-seq data from human and mouse tissues in normal and disease states. CellCommuNet currently includes 376 single datasets from multiple sources, and 118 comparison datasets between disease and normal samples originating from the same study. CellCommuNet provides information on the strength of communication between cells and related signalling pathways and facilitates the exploration of differences in cell-cell communication between healthy and disease states. Users can also search for specific signalling pathways, ligand-receptor pairs, and cell types of interest. CellCommuNet provides interactive graphics illustrating cell-cell communication in different states, enabling differential analysis of communication strength between disease and control samples. This comprehensive database aims to be a valuable resource for biologists studying cell-cell communication networks.

DiSignAtlas: an atlas of human and mouse disease signatures based on bulk and single-cell transcriptomics.

Molecular signatures are usually sets of biomolecules that can serve as diagnostic, prognostic, predictive, or therapeutic markers for a specific disease. Omics data derived from various high-throughput molecular biology technologies offer global, unbiased and appropriately comparable data, which can be used to identify such molecular signatures. To address the need for comprehensive disease signatures, DiSignAtlas (http://www.inbirg.com/disignatlas/) was developed to provide transcriptomics-based signatures for a wide range of diseases. A total of 181 434 transcriptome profiles were manually curated from studies involving 1836 nonredundant disease types in humans and mice. Then, 10 306 comparison datasets comprising both disease and control samples, including 328 single-cell RNA sequencing datasets, were established. Furthermore, a total of 3 775 317 differentially expressed genes in humans and 1 723 674 in mice were identified as disease signatures by analysing transcriptome profiles using commonly used pipelines. In addition to providing multiple methods for the retrieval of disease signatures, DiSignAtlas provides downstream functional enrichment analysis, cell type analysis and signature correlation analysis between diseases or species when available. Moreover, multiple analytical and comparison tools for disease signatures are available. DiSignAtlas is expected to become a valuable resource for both bioscientists and bioinformaticians engaged in translational research.