A γδ T cell-IL-3 axis controls allergic responses through sensory neurons.

In naive individuals, sensory neurons directly detect and respond to allergens, leading to both the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch. Although these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naive state is unknown.

Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma.

Interplay between chromatin-associated complexes and modifications critically contribute to the partitioning of epigenome into stable and functionally distinct domains. Yet there is a lack of systematic identification of chromatin crosstalk mechanisms, limiting our understanding of the dynamic transition between chromatin states during development and disease. Here we perform co-dependency mapping of genes using CRISPR-Cas9-mediated fitness screens in pan-cancer cell lines to quantify gene-gene functional relationships.

Histone methylation antagonism drives tumor immune evasion in squamous cell carcinomas.

How cancer-associated chromatin abnormalities shape tumor-immune interaction remains incompletely understood. Recent studies have linked DNA hypomethylation and de-repression of retrotransposons to anti-tumor immunity through the induction of interferon response. Here, we report that inactivation of the histone H3K36 methyltransferase NSD1, which is frequently found in squamous cell carcinomas (SCCs) and induces DNA hypomethylation, unexpectedly results in diminished tumor immune infiltration.

The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape.

Enzymes that catalyse CpG methylation in DNA, including the DNA methyltransferases 1 (DNMT1), 3A (DNMT3A) and 3B (DNMT3B), are indispensable for mammalian tissue development and homeostasis. They are also implicated in human developmental disorders and cancers, supporting the critical role of DNA methylation in the specification and maintenance of cell fate. Previous studies have suggested that post-translational modifications of histones are involved in specifying patterns of DNA methyltransferase localization and DNA methylation at promoters and actively transcribed gene bodies.

Automated quantitative image analysis for ex vivo metastasis assays reveals differing lung composition requirements for metastasis suppression by KISS1.

Imaging is broadly used in biomedical research, but signal variation complicates automated analysis. Using the Pulmonary Metastasis Assay (PuMA) to study metastatic colonization by the metastasis suppressor KISS1, we cultured GFP-expressing melanoma cells in living mouse lung ex vivo for 3 weeks. Epifluorescence images of cells were used to measure growth, creating large datasets which were time consuming and challenging to quantify manually due to scattering of light from outside the focal plane.