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.

10x Genomics is participating in Morgan Stanley's Annual Global Healthcare Conference on Sep 10, showcasing its leadership in single-cell biology.

Accurate cell type annotation is a major challenge in single-cell and spatial omics. Here, authors present a user-friendly platform providing robust automatic annotation and enhanced biological interp...

1Cell.Ai has partnered with BioSkryb to revolutionize single cell multi-omics, enabling unprecedented accuracy in detecting rare mutations in cell research.

Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined. Here, utilizing scRNA-seq data for Glioma primary tumors from 85 human tumors, we extracted 183,062 myeloid cells and discovered that nearly all glioma-associated myeloid cells express at least one of four immunomodulatory activity programs. These include a Scavenger Immunosuppressive program, a Complement Immunosuppressive program, a Microglial Inflammatory program, and a Systemic inflammatory program. Integration of mitochondrial DNA-based lineage tracing, spatial transcriptomics, and functional organoid models reveals that these programs are driven by microenvironmental cues and therapies rather than myeloid cell type or origin. All four programs are present in lower-grade and high-grade gliomas and expressed in multiple myeloid cell types derived from blood or resident myeloid cell origins. The Scavenger Immunosuppressive program is induced in hypoxic regions, while the Complement Immunosuppressive program is driven by dexamethasone. Both immunosuppressive programs are less prevalent in lower-grade gliomas, which are instead enriched for the Microglial Inflammatory program. We validated this striking myeloid cell plasticity by demonstrating that application of peripheral blood monocytes to glioma organoid models leads to de novo induction of microglia, macrophage and dendritic cell identities, and all four immunomodulatory programs. Our study provides a resource and new framework to understand immunomodulatory myeloid cells in glioma, and a foundation to develop effective immunotherapy strategies for glioma patients.

10x Genomics showcases cutting-edge advancements in single cell and spatial biology at the AGBT General Meeting, enhancing research efficiency.

10x Genomics announces its preliminary results for Q4 and full year 2024, showcasing growth in revenue amid challenges in instrument sales.

Molecular Ecology is an international journal for research using molecular genetic techniques to address questions in ecology, evolution, behavior and conservation.