FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal

Drosophila neuroblasts (NBs) have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type-specific gene expression data. Here, we describe a method for isolating large numbers of pure NBs and differentiating neurons that retain both cell-cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted NB-specific transcription factors that can be arranged in a network containing hubs for Notch signaling, growth control, and chromatin regulation. Overexpression and RNA interference for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klumpfuss function causes premature differentiation and that overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for investigating Drosophila developmental neurobiology, and the described method can be applied to other invertebrate stem cell lineages as well

Targeted transgenic RNAi knockdown of cell fate determinants induces neoplastic tumor growth and metastasis in a Drosophila transplantation model of neural stem cell derived cancer

Genetic models such as Drosophila have sophisticated transgenic and molecular genetic tools available to investigate proliferation control in normal and tumorigenic neural stem cells. In this report, we adapted a targeted transgenic RNAi knockdown approach based on the Gal4/UAS expression system to the study of neoplastic tumor formation and metastatic growth in the Drosophila brain tissue transplantation model. Transgenic RNAi driven knockdown of numb, brain tumor (brat) and prospero (pros) in all neuroblasts (type I and type II) resulted in a high incidence of neoplastic tumor formation after transplantation that was comparable to that of loss-of-function mutations in these cell fate determinants. RNAi knockdown of numb and brat specifically restricted to type II neuroblast lineages also resulted in tumor formation after transplantation. A marked temperature dependence of tumor formation after transplantation was documented and quantified for RNAi-induced knockdown of numb, brat and pros. An in vivo assay for micrometastasis formation in ovarioles revealed significant metastatic potential of transplanted overproliferating brain tissue induced by RNAi knockdown of these cell fate determinants. These findings establish the foundation for RNAi-based investigations of the mechanisms which underlie the proliferation, invasion and metastastic potential of neural stem cell induced tumors in the Drosophila model

The asymmetrically segregating lncRNA cherub is required for transforming stem cells into malignant cells

Tumor cells display features that are not found in healthy cells. How they become immortal and how their specific features can be exploited to combat tumorigenesis are key questions in tumor biology. Here we describe the long non-coding RNA cherub that is critically required for the development of brain tumors in; Drosophila; but is dispensable for normal development. In mitotic; Drosophila; neural stem cells, cherub localizes to the cell periphery and segregates into the differentiating daughter cell. During tumorigenesis, de-differentiation of cherub-high cells leads to the formation of tumorigenic stem cells that accumulate abnormally high cherub levels. We show that cherub establishes a molecular link between the RNA-binding proteins Staufen and Syncrip. As Syncrip is part of the molecular machinery specifying temporal identity in neural stem cells, we propose that tumor cells proliferate indefinitely, because cherub accumulation no longer allows them to complete their temporal neurogenesis program

The World Health Organization COVID-19 surveillance database

Abstract In January 2020, SARS-CoV-2 virus was identified as a cause of an outbreak in China. The disease quickly spread worldwide, and the World Health Organization (WHO) declared the pandemic in March 2020. From the first notifications of spread of the disease, the WHO’s Emergency Programme implemented a global COVID-19 surveillance system in coordination with all WHO regional offices. The system aimed to monitor the spread of the epidemic over countries and across population groups, severity of the disease and risk factors, and the impact of control measures. COVID-19 surveillance data reported to WHO is a combination of case-based data and weekly aggregated data, focusing on a minimum global dataset for cases and deaths including disaggregation by age, sex, occupation as a Health Care Worker, as well as number of cases tested, and number of cases newly admitted for hospitalization. These disaggregations aim to monitor inequities in COVID-19 distribution and risk factors among population groups. SARS-CoV-2 epidemic waves continue to sweep the world; as of March 2022, over 445 million cases and 6 million deaths have been reported worldwide. Of these, over 327 million cases (74%) have been reported in the WHO surveillance database, of which 255 million cases (57%) are disaggregated by age and sex. A public dashboard has been made available to visualize trends, age distributions, sex ratios, along with testing and hospitalization rates. It includes a feature to download the underlying dataset. This paper will describe the data flows, database, and frontend public dashboard, as well as the challenges experienced in data acquisition, curation and compilation and the lessons learnt in overcoming these. Two years after the pandemic was declared, COVID-19 continues to spread and is still considered a Public Health Emergency of International Concern (PHEIC). While WHO regional and country offices have demonstrated tremendous adaptability and commitment to process COVID-19 surveillance data, lessons learnt from this major event will serve to enhance capacity and preparedness at every level, as well as institutional empowerment that may lead to greater sharing of public health evidence during a PHEIC, with a focus on equity