'Ettore Majorana' Foundation and International Centre for Scientific Culture Schools

Human trophoblasts activate a DUX4-driven antiviral program in response to herpesvirus infection. This defense pathway, distinct from canonical immune resp

Epstein-Barr virus (EBV) is a very common herpesvirus that infects more than 90% of the general population. Epidemiologic data indicate that EBV is a requisite risk factor for the development of multi...

Understanding porcine placental development has been hindered by the lack of in vitro models that reflect its cellular heterogeneity. This study develops a swine trophoblast organoid model that mimics...

Granulomas are classic manifestations of tuberculosis pathogenesis. They result from an ensemble of immune responses to Mycobacterium tuberculosis infection, but the identities, arrangement, cellular interactions, and regulation of the cells that comprise them have thus far been incompletely understood. To better understand the composition of granulomas, we conducted spatial and single-cell RNA sequencing of granulomas in biopsy specimens from patients with tuberculosis. We found that granulomas consist of concentric transcriptional laminae surrounding areas of central necrosis. We identified distinct populations of granuloma-associated stromal cells, fibroblasts, lymphocytes, mast cells, dendritic cells, neutrophils, and macrophages. Furthermore, gene expression among these cell populations differed by location within granulomas. We used inferential analysis to predict dominant granuloma cell-cell interactions, the activity of major signaling pathways, and transcription factor activities. Using spatial deconvolution, we mapped a conserved pattern of cellular organization dominated by macrophages rich in SPP1/osteopontin expression. Trajectory analysis of macrophage subtypes mapped their differentiation and supported the importance of SPP1 to granuloma macrophage polarization. Using the Mycobacterium marinum-zebrafish model, we found that mycobacterial infection induces spp1 expression in macrophages and that spp1 ablation results in granuloma formation defects and reduced survival in adult animals. Cumulatively, we have identified a dominant macrophage granuloma population as well as its central regulatory gene in human samples and confirmed the importance of spp1 to granuloma biology in vivo.

Advanced genetic sequencing reveals the cells behind many persistent tuberculosis infections and provides a map of exactly where these cells live, pointing the way toward new treatments.

Advanced genetic sequencing reveals the cells behind many persistent tuberculosis infections and provides a map of exactly where these cells live, pointing the way toward new treatments.

This step-by-step tutorial demonstrates how to leverage single cell RNA-seq data to annotate Xenium In Situ data using label transfer. It includes thorough instructions for selecting references, prepr...