Processing single-cell RNA-seq datasets using SingCellaR

Single-cell RNA sequencing has led to unprecedented levels of data complexity. Although several computational platforms are available, performing data analyses for multiple datasets remains a significant challenge. Here, we provide a comprehensive analytical protocol to interrogate multiple datasets on SingCellaR, an analysis package in R. This tool can be applied to general single-cell transcriptome analyses. We demonstrate steps for data analyses and visualization using bespoke pipelines, in conjunction with existing analysis tools to study human hematopoietic stem and progenitor cells. For complete details on the use and execution of this protocol, please refer to Roy et al. (2021)

Associations between hedonic hunger and BMI during a two-year behavioural weight loss trial.

ObjectiveProspective studies on relationships between hedonic hunger and BMI (Body Mass Index) during weight management are lacking. This study examined if hedonic hunger reduced during a behavioural weight management programme, and if hedonic hunger predicted future BMI.MethodsParticipants were 594 community-dwelling, UK-based adults(396 female; age 56.43 years, s.d. = 12.50, range 20-83 years); 490 participants (82.5%) had obesity. Participants were randomised to a 12- or 52-week behavioural weight management intervention (WW12 or WW52, respectively) or a brief self-help intervention (BI). Relationships between hedonic hunger and BMI over 24 months (baseline, 3, 12, 24 months) were analysed using an autoregressive cross-lagged model.ResultsHedonic hunger scores decreased from 2.71 (s.d. = .91) at baseline to 2.41 (s.d. = .88) at 3 months (p .05). Baseline hedonic hunger scores predicted 3-month scores (B = .76, SE = .03, p .05). BMI at 12 months was lower in WW52 30.87kg/m2, s.d. = 5.02) than WW12 (32.12 kg/m2, s.d. = 5.58, p = .02, CI .16 to 2.34) and BI (32.74 kg/m2, s.d. = 4.15, p = .01, CI .30 to 3.45). BMI was not affected by intervention at any other time point (p's>.05).ConclusionHedonic hunger reduced during weight management irrespective of intervention. Early reductions in hedonic hunger appear to be associated with lower BMI in the medium-term. Identifying ways to reduce hedonic hunger during weight loss could aid weight management for some people

Does urban agriculture contribute to food security, and how might this be achieved?

Food system challenges exacerbate inequalities in access to fresh healthy food and threaten food security. Lack of food security, referred to as food insecurity, is associated with poorer physical and mental health outcomes and has been identified as a key challenge to address by calls for food system transformation. Increasing food production through urban agriculture, the production of fruit and vegetables in urban areas, has been identified as a potentially effective contributor to food system transformation, but the effect of this on household or UK-level food security is unclear. This paper reviews international evidence of urban agriculture's impact on food security. While findings are mixed, available evidence suggests that urban agriculture makes a modest, yet positive, contribution to food security by facilitating the availability of and access to fresh fruit and vegetables to food insecure households. In the UK, studies have shown this to be particularly beneficial during times of food system disruption. Capitalising on such benefits to improve food security requires government investment and support at both the national and local level, therefore increasing access to land for food growing, reducing costs of related resources, and collaboration with existing community groups to enhance sharing of skills and expertise, are identified as avenues for exploration that may help to achieve this. This review also highlights opportunities for future research in this field that may strengthen the quality of the evidence supporting urban agriculture's impact on food security

Growing your own in times of crisis: the role of home food growing in perceived food insecurity and well-being during the early COVID-19 lockdown

Household food insecurity and poor well-being have increased during the coronavirus disease 2019 (COVID-19) pandemic and resulting lockdown measures. Home food growing has been associated with improved food access and well-being, but it is unknown what role it plays during food supply crises and lockdown. It is also unclear how home food growing and social restrictions may affect opinions about growing food in urban areas (i.e., urban agriculture [UA]). A cross-sectional online survey was conducted during the UK national lockdown in March-April 2020 to measure home food growing, perceived food insecurity, well-being, and opinions of UA. The participants were 477 UK-based adults (369 female, mean age 39.57 years ± 13.36); 152 participants were engaged in home food growing prior to the pandemic. Responses were compared to data collected from a separate sample of participants before the pandemic (N = 583) to explore potential shifts in opinions about UA. Participants who engaged in home food growing had lower levels of food insecurity (U ­= 19894.50, z = -3.649, p<.001, r = -.167) and higher well-being (U = 19566.50, z = -3.666, p<.001, r = -.168) than those not engaged in home food growing. Perceived food insecurity partially mediated the relationship between home food growing and well-being; home food growing was associated with less food insecurity, which in turn was associated with better well-being. There were no differences in opinions of UA compared to the sample of participants from before the pandemic. Home food growing may have had a protective effect over perceived food security and well-being in the early stages the pandemic. Opinions of UA were positive and unchanged compared to data collected pre-pandemic. Policies that support home food growing and access to suitable growing spaces and resources may be beneficial for food system resilience and well-being.Biotechnology and Biological Sciences Research Council (BBSRC): BB/S01425X/1, ESRC, NERC and the Scottish Governmen

Potential of urban green spaces for supporting horticultural production: a national scale analysis

As urban areas and land-use constraints grow, there is increasing interest in utilizing urban spaces for food production. Several studies have uncovered significant potential for urban growing to supplement production of fruit and vegetables, focusing on one or two cities as case studies, whilst others have assessed the global scale potential. Here, we provide a national-scale analysis of the horticultural production potential of urban green spaces, which is a relevant scale for agri-food and urban development policy making using Great Britain (GB) as a case study. Urban green spaces available for horticultural production across GB are identified and potential yields quantified based on three production options. The distribution of urban green spaces within 26 urban towns and cities across GB are then examined to understand the productive potential compared to their total extent and populations. Urban green spaces in GB, at their upper limit, have the capacity to support production that is 8× greater than current domestic production of fruit and vegetables. This amounts to 38% of current domestic production and imports combined, or >400% if exotic fruits and vegetables less suited to GB growing conditions are excluded. Most urban green spaces nationally are found to fall within a small number of categories, with private residential gardens and amenity spaces making up the majority of space. By examining towns and cities across GB in further detail, we find that the area of green space does not vary greatly between urban conurbations of different sizes, and all are found to have substantial potential to meet the dietary needs of the local urban population. This study highlights that national policies can be suitably developed to support urban agriculture and that making use of urban green spaces for food production could help to enhance the resilience of the national-scale food system to shocks in import pathways, or disruptions to domestic production and distribution.Biotechnology and Biological Sciences Research Council (BBSRC): BB/S01425X/1, ESRC and NERC Scottish Governmen

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients (‘chr21amp’). We report that chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. The chr21amp event is highly clonal and present throughout the hematopoietic hierarchy. DYRK1A, a serine threonine kinase and transcription factor, is the only gene in the 2.7Mb minimally amplified region which showed both increased expression and chromatin accessibility compared to non-chr21amp BP-MPN controls. We demonstrate that DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development, including DNA repair, STAT signalling and BCL2 overexpression. DYRK1A is essential for BP-MPN cell proliferation in vitro and in vivo, and DYRK1A inhibition synergises with BCL2 targeting to induce BP-MPN cell apoptosis. Collectively, these findings define the chr21amp event as a prognostic biomarker in BP-MPN and link chromothripsis to a druggable target

Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

Understanding the genetic and nongenetic determinants of tumor protein 53 (TP53)-mutation-driven clonal evolution and subsequent transformation is a crucial step toward the design of rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis of hematopoietic stem/progenitor cells (HSPCs) from patients with a myeloproliferative neoplasm who transform to TP53-mutant secondary acute myeloid leukemia (sAML). All patients showed dominant TP53 ‘multihit’ HSPC clones at transformation, with a leukemia stem cell transcriptional signature strongly predictive of adverse outcomes in independent cohorts, across both TP53-mutant and wild-type (WT) AML. Through analysis of serial samples, antecedent TP53-heterozygous clones and in vivo perturbations, we demonstrate a hitherto unrecognized effect of chronic inflammation, which suppressed TP53 WT HSPCs while enhancing the fitness advantage of TP53-mutant cells and promoted genetic evolution. Our findings will facilitate the development of risk-stratification, early detection and treatment strategies for TP53-mutant leukemia, and are of broad relevance to other cancer types