Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism.

Secreted extracellular vesicles (EVs) influence the tumor microenvironment and promote distal metastasis. Here, we analyzed the involvement of melanoma-secreted EVs in lymph node pre-metastatic niche formation in murine models. We found that small EVs (sEVs) derived from metastatic melanoma cell lines were enriched in nerve growth factor receptor (NGFR, p75NTR), spread through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis.

Isolation of exophers from cardiomyocyte-reporter mouse strains by fluorescence-activated cell sorting.

Cardiac exophers are membrane-bound extracellular vesicles released by cardiomyocytes with varied content and an average diameter of 3.5 μm. Here, we provide a detailed protocol to enable the identification and purification of cardiomyocyte-derived exophers by using fluorescence-activated cell sorting for downstream cellular and molecular analysis.

Co-option of Neutrophil Fates by Tissue Environments.

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues.

Mitochondrial Adaptations in the Growing Heart.

The heart pumps blood throughout the whole life of an organism, without rest periods during which to replenish energy or detoxify. Hence, cardiomyocytes, the working units of the heart, have mechanisms to ensure constitutive production of energy and detoxification to preserve fitness and function for decades. Even more challenging, the heart must adapt to the varying conditions of the organism from fetal life to adulthood, old age, and pathological stress.

Locally renewing resident synovial macrophages provide a protective barrier for the joint.

Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis.

Specialized functions of resident macrophages in brain and heart.

The functions of macrophages in healthy tissues extend beyond their well-established roles as immune sentinels and effectors. Among tissues, cells of the brain and heart possess unique excitatory properties that likely demand special support. Accordingly, existing evidence demonstrates that microglia in the brain has an active role in synaptic organization, control of neuronal excitability, phagocytic removal of debris, and trophic support during brain development.

Neutrophils in Homeostasis, Immunity, and Cancer.

Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation.