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Single-Cell Transcriptome Study Suggests Dual Pathways Behind in Immune Neoplasm

For a paper in Science Immunology, an international team led by investigators at the Karolinska Institute describes two lineages of Langerhans cell histiocytosis (LCH) lesions — an immune neoplasm marked by altered MAP kinase signaling pathway activity and mononuclear phagocyte differentiation problems. Using single-cell RNA sequencing, high-dimensional microscopy, lineage tracing, and other analyses, the researchers compared LCH cells to one another and to non-neoplastic mononuclear phagocyte cells in the microenvironment, detecting distinct dendritic cell (DC) clusters resembling so-called DC2 or DC3/monocyte-like cells and LCH-driving interactions between them that were facilitated by Notch-dependent signaling. "Our data support the premise of Notch-dependent cross-talk between DC2 and DC3/monocyte lineages and show that cooperativity between these lineages has the capacity to promote the pathognomonic LCH program," the authors suggest, calling it a "convergent dual origin model of LCH."