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Inflammatory Mesenchymal Stromal Cells and IFN-responsive T cells are key mediators of human bone marrow niche remodeling in CHIP and MDS

Prummel, K. D.; Woods, K.; Kholmatov, M.; Schmitt, E.; Vlachou, E. P.; Poschmann, G.; Stuhler, K.; Wehner, R.; Schmitz, M.; Winter, S.; Oelschlaegel, U.; Schwartz, L. S.; Moura, P. L.; Hellstrom-Lindberg, E.; Theobald, M.; Trowbridge, J. J.; Platzbecker, U.; Zaugg, J. B.; Guezguez, B.

2024-11-27 molecular biology
10.1101/2024.11.27.625734 bioRxiv
Show abstract

Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP), potentially progressing to myelodysplastic syndromes (MDS). Here, we investigated how CHIP and MDS remodel the human bone marrow (BM) niche relative to healthy elderly donors, using single cell and anatomical analyses in a large BM cohort. We found distinct inflammatory remodeling of the BM in CHIP and MDS. Furthermore, the stromal compartment progressively lost its HSPC-supportive adipogenic CXCL12-abundant reticular cells while an inflammatory mesenchymal stroma cell (iMSCs) population emerged in CHIP, which expanded in MDS. iMSCs exhibited distinct functional signatures in CHIP and MDS, retaining residual HSPC-support and angiogenic activity in MDS, corresponding with an increase in microvasculature in the MDS niche. Additionally, an IFN-responsive T cell population was linked to fueling inflammation in the stroma. Overall, these findings open new avenues for early intervention in hematological malignancies.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.