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Comprehensive single cell RNA profiling of the spleen in murine myelofibrosis identifies targetable immune-stromal interactions

GSE336713 Mus musculus Expression profiling by high throughput sequencing 5 samples Submitted 2026/07/01 Platform GPL24247
Summary
Splenomegaly is a defining feature of myelofibrosis, yet the contribution of splenic mesenchymal stroma to disease progression remains unclear. We perferomed spatial transcriptomics of murine spleens to map extramedullary hematopoiesis niches. Activated red pulp reticular cells localize near hematopoietic stem and progenitor cells, and early disease shows marginal zone disruption with lymphoid depletion preceding stromal remodeling. Trajectory analyses reveal a shift of reticular cells from hematopoiesis-supportive to inflammatory and pro-fibrotic states driven by macrophage- and megakaryocyte-derived signals that activate complement and induce TNFα, TGF-β, extracellular matrix, and Thbs1 programs. Stromal deletion or pharmacological inhibition of complement component C3 suppresses these pathways, restores splenic architecture, and reduces splenomegaly and bone marrow fibrosis. These findings identify complement-dependent stromal reprogramming as a mechanism governing hematopoietic niches and a targetable axis in myelofibrosis.
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Also filed as BioProject PRJNA1482447 and SRA study SRP712895. Searching any of these in the dataset finder brings you back here.

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