Advances in the Application of Single-Cell Transcriptomics in Plant Systems and Synthetic Biology.

Plants are complex systems hierarchically organized and composed of various cell types. To understand the molecular underpinnings of complex plant systems, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for revealing high resolution of gene expression patterns at the cellular level and investigating the cell-type heterogeneity. Furthermore, scRNA-seq analysis of plant biosystems has great potential for generating new knowledge to inform plant biosystems design and synthetic biology, which aims to modify plants genetically/epigenetically through genome editing, engineering, or re-writing based on rational design for increasing crop yield and quality, promoting the bioeconomy and enhancing environmental sustainability. In particular, data from scRNA-seq studies can be utilized to facilitate the development of high-precision Build-Design-Test-Learn capabilities for maximizing the targeted performance of engineered plant biosystems while minimizing unintended side effects. To date, scRNA-seq has been demonstrated in a limited number of plant species, including model plants (e.g., Arabidopsis thaliana), agricultural crops (e.g., Oryza sativa), and bioenergy crops (e.g., Populus spp.). It is expected that future technical advancements will reduce the cost of scRNA-seq and consequently accelerate the application of this emerging technology in plants. In this review, we summarize current technical advancements in plant scRNA-seq, including sample preparation, sequencing, and data analysis, to provide guidance on how to choose the appropriate scRNA-seq methods for different types of plant samples. We then highlight various applications of scRNA-seq in both plant systems biology and plant synthetic biology research. Finally, we discuss the challenges and opportunities for the application of scRNA-seq in plants.

Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky.

Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.

The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells.

The intracellular cholesterol transporter NPC1 functions in late endosomes and lysosomes to efflux unesterified cholesterol, and its deficiency causes Niemann-Pick disease Type C, an autosomal recessive lysosomal disorder characterized by progressive neurodegeneration and early death. Here, we use single-nucleus RNA-seq on the forebrain of Npc1-/- mice at P16 to identify cell types and pathways affected early in pathogenesis. Our analysis uncovers significant transcriptional changes in the oligodendrocyte lineage during developmental myelination, accompanied by diminished maturation of myelinating oligodendrocytes. We identify upregulation of genes associated with neurogenesis and synapse formation in Npc1-/- oligodendrocyte lineage cells, reflecting diminished gene silencing by H3K27me3. Npc1-/- oligodendrocyte progenitor cells reproduce impaired maturation in vitro, and this phenotype is rescued by treatment with GSK-J4, a small molecule inhibitor of H3K27 demethylases. Moreover, mobilizing stored cholesterol in Npc1-/- mice by a single administration of 2-hydroxypropyl-ß-cyclodextrin at P7 rescues myelination, epigenetic marks, and oligodendrocyte gene expression. Our findings highlight an important role for NPC1 in oligodendrocyte lineage maturation and epigenetic regulation, and identify potential targets for therapeutic intervention.

Willingness of children and adolescents to have a COVID-19 vaccination: Results of a large whole schools survey in England.

BACKGROUND: Vaccine hesitancy has affected COVID-19 adult vaccination programs in many countries. Data on hesitancy amongst child and adolescent populations is largely confined to parent opinion. We investigated the characteristics of vaccine hesitant children and adolescents using results from a large, school-based self-report survey of the willingness to have a COVID-19 vaccination in students aged 9 -18 years in England. METHODS: Data from the OxWell Student Survey on mental health, life experiences and behaviours were used, collected from four counties across England. Local authority partners recruited schools. The vaccine hesitancy question gave six response options and were clustered to inform delivery: eager and willing were categorised as vaccination 'opt-in', don't know and not bothered categorised as 'undecided', and unwilling and anti-vaccination categorised as 'opt-out'. We conducted a multinomial regression to determine associations between vaccine hesitancy and sociodemographic, health behaviour and social connection variables. FINDINGS: 27,910 students from 180 schools answered the vaccine hesitancy question between 14th May and 21st July 2021, of whom 13984 (50.1%) would opt-in to take a vaccination, 10322 (37.0%) were undecided, and 3604 (12.9%) would opt-out. A lower percentage of younger students reported that they would opt-in to vaccination, for example, 35.7% of 9-year-olds and 51.3% of 13-year-olds compared to 77.8% of 17-year-olds would opt-in to take a vaccination. Students who were 'opt-out' or 'undecided' (a combined 'vaccine hesitant' group) were more likely to come from deprived socioeconomic contexts with higher rates of home rental versus home ownership and their school locations were more likely to be in areas of greater deprivation. They were more likely to smoke or vape, spend longer on social media, feel that they did not belong in their school community but had lower levels of anxiety and depression. The vaccine hesitant students- the undecided and opt-out groups- were similar in profile, although the opt-out students had higher reported confirmed or probable previous COVID-19 infection than the opt-in group, whereas those undecided, did not. INTERPRETATION: If government vaccination strategies move towards vaccinating younger school-aged students, efforts to increase vaccination uptake may be necessary. Compared with students who would opt-in, those who were vaccine hesitant had greater indicators of social deprivation and felt a lack of community cohesion by not feeling a sense of belonging at their school. There were indications that those students who would opt-out had higher levels of marginalisation and mistrust. If programmes are rolled out, focus on hesitant younger students will be important, targeting more marginalised and deprived young people with information from trusted sources utilising social media; improving access to vaccination centres with provision both in and outside school; and addressing fears and worries about the effects of the vaccine. The main limitation of this study is that the participant group may not be wholly representative of England or the UK, which may bias population-level estimates of willingness to be vaccinated. FUNDING: The Westminster Foundation, the National Institute for Health Research (NIHR) Applied Research Collaboration Oxford and Thames Valley at Oxford Health NHS Foundation Trust and the NIHR Oxford Health Biomedical Research Centre.

Controllable synthesis of patchy particles with tunable geometry and orthogonal chemistry.

HYPOTHESIS: Self-assembly using anisotropic colloidal building blocks may lead to superstructures similar to those found in molecular systems yet can have unique optical, electronic, and structural properties. To widen the spectrum of achievable superstructures and related properties, significant effort was devoted to the synthesis of new types of colloidal particles. Despite these efforts, the preparation of anisotropic colloids carrying chemically orthogonal anchor groups on distinct surface patches remains an elusive challenge. EXPERIMENTS: We report a simple yet effective method for synthesizing patchy particles via seed-mediated heterogeneous nucleation. Key to this procedure is the use of 3-(trimethoxysilyl)propyl methacrylate (TPM) or 3-(trimethoxysilyl)propyl acrylate (TMSPA), which can form patches on a variety of functional polymer seeds via a nucleation and growth mechanism. FINDINGS: A family of anisotropic colloids with tunable numbers of patches and patch arrangements were prepared. By continuously feeding TPM or TMSPA the geometry of the colloids could be adjusted accurately. Furthermore, the patches could be reshaped by selectively polymerizing and/or solvating the individual colloidal compartments. Relying on the chemically distinct properties of the TPM/TMSPA and seed-derived domains, both types of patches could be functionalized independently. Combining detailed control over the patch chemistry and geometry opens new avenues for colloidal self-assembly.

Integrated care to address child and adolescent health in the 21st century: A clinical review.

Background: Increasing specialisation and technical sophistication of medical tools across the 21st century have contributed to dramatic improvements in the life-expectancy of children and adolescents with complex physical health problems. Concurrently, there is growing appreciation within the community of the extent that children and adolescents experience mental disorders, which are more prevalent in those with complex chronic, serious or life-limiting health conditions. In this context, there are compelling reasons for paediatric services to move to a model of care that promotes greater integration of child psychiatry within the medical, somatic teams that care for children and adolescents in children's hospitals. Aims: In this article, we discuss the range of medical disorders managed by contemporary paediatrics. Materials and Methods: We conducted a broad review of the literature and existing services, and use individual accounts to illustrate adolescents' healthcare preferences in the context of the challenges they experience around their mental health. Results: Relevant disorders include life-limiting disorders, such as cancer; disorders involving the brain, such as epilepsy; common chronic disorders, such as asthma and diabetes; psychiatric emergencies, such as deliberate self-harm; and conditions that most commonly present to paediatric services, but where psychiatric input is required, such as severe eating disorders, somatic symptom disorders and gender dysphoria. The persisting legacy of the historical separation of physical and mental health services is described. Yet there are many models of service integration that can promote more collaborative care between psychiatrists and medical specialists, including some which have been taken to scale. Discussion: In essence, clinical teams in children's hospitals require more collaborative approaches that facilitate early recognition and treatment of the psychological aspects of illness as an integral part of patient-centred, family-focussed paediatric care, rather than as something that is bolted on when things go wrong. Conclusion: Whilst trust and goodwill between services and providers will be required for novel models of care to be implemented, evaluation of these new models and incorporation of young people's healthcare preferences is needed.