Issues

Summary: Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Here, we discuss recent advances in genome editing and challenges in using these techniques to assess variant function in primary hematopoietic cells.

Summary: The success of genetic studies provides a unique opportunity to better understand immune-mediated disease mechanisms. To achieve this, however, knowledge of where disease-associated variants lie must be translated into an understanding of how they cause disease.

Summary: Using a Drosophila Ras-driven cancer model, inhibitors of diacyl glycerol kinase α (DGKα) were identified as being synergistic with low doses of the Ras pathway inhibitor, trametinib.

Summary: This extensive study provides progress in the development of synthetic modulators of HuR functions, their genome-wide mechanism of action and their activity as anti-inflammatory agents.

Summary: This study shows, for the first time, a role for NLGN3 in GnRH neuritogenesis and reveals a common genetic mechanism between GnRH deficiency and autism, by applying a combined multiomic approach.

Summary: Limb defects in Robinow syndrome are associated with mutations in FZD2. Using mouse models, we show that FZD2 is causative, and controls limb development via both canonical and non-canonical Wnt pathways.

Summary: We identify a dual mechanism of spina bifida in Zic2 mutant mice – a possible paradigm for multifactorial human defects. BMP overactivation prevents neuroepithelial bending, whereas RhoA overactivation causes actomyosin accumulation.

Summary: This study uses zebrafish embryos and homology-directed gene editing to investigate the effect of activated PI3 kinase delta syndrome 1 mutations on innate immune cells, observing neutrophilia without defects in neutrophil differentiation or migration.

Summary: Using a preclinical Alzheimer's disease model, our work highlights that episodic memory impairment at early disease stage is associated with neuronal hyperactivity in specific medial prefrontal cortex and hippocampus regions.

Editor's choice: Our work using in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells shows a hepatoprotective role of peritumoral hepatic stellate cells in liver tumorigenesis.

Summary: We describe an in vivo quantitative high-throughput screening strategy with C. elegans, designed to leverage and engage experience of the model organism community with screening and drug development resources.

Summary: Description and demonstration of an automated easy-to-use online tool for classifying intestinal organoids to facilitate quantitative analyses of increasingly popular organoids.