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Omics · study · 2026

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

Listed in NCBI GEO

Splenomegaly is a defining feature of myelofibrosis, yet the contribution of splenic mesenchymal stroma to disease progression remains unclear.

Description

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.

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These findings identify complement-dependent stromal reprogramming as a mechanism governing hematopoietic niches and a targetable axis in myelofibrosis.

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Life Sciences
Inferred from text
Biochemistry and cell biology 70% · Disease 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33671313 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].anzsrc:group:3101enrichment · NCBI GEOtaxonomy-embedding@1.1.0title+keywords+description (70%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title