Document Type
Article
Publication Date
11-18-2025
Original Citation
Prummel K,
Woods K,
Kholmatov M,
Schmitt E,
Vlachou E,
Labyadh M,
Wehner R,
Poschmann G,
Stühler K,
Winter S,
Oelschlaegel U,
Wobus M,
Schwartz L,
Moura P,
Hellström-Lindberg E,
Rajalingam K,
Theobald M,
Trowbridge JJ,
Carron C,
Jaffredo T,
Schmitz M,
Platzbecker U,
Zaugg J,
Guezguez B.
Inflammatory stromal and T cells mediate human bone marrow niche remodeling in clonal hematopoiesis and myelodysplasia. Nat Commun. 2025;16(1):10042.
Keywords
JMG, Humans, Myelodysplastic Syndromes, Clonal Hematopoiesis, Hematopoietic Stem Cells, Mesenchymal Stem Cells, T-Lymphocytes, Stem Cell Niche, Bone Marrow, Inflammation, Coculture Techniques, Aged, Female, Male, Middle Aged, Hematopoiesis, Chemokine CXCL12
JAX Source
Nat Commun. 2025;16(1):10042.
ISSN
2041-1723
PMID
41253811
DOI
https://doi.org/10.1038/s41467-025-65803-y
Abstract
Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP) and progression to myelodysplastic syndromes (MDS). Using single-cell and anatomical profiling of a large cohort of human bone marrow (BM), we show that the HSPC BM niche in CHIP and MDS is undergoing inflammatory remodeling. This includes loss of CXCL12⁺ adipogenic stromal cells and the emergence of a distinct population of inflammatory mesenchymal stromal cells (iMSCs), which arise in CHIP and become more prevalent in MDS. Functional studies in primary BM HSPC-MSC co-cultures reveals that healthy aged and CHIP HSPCs activate stromal support, while MDS HSPCs fail to do so. In contrast, MDS blasts further suppress HSPC support and trigger inflammation, indicating disease-stage-specific stromal disruption. In parallel, we show that iMSCs retain partial support and angiogenic potential in MDS, coinciding with expanded BM vasculature. Additionally, we identify IFN-responsive T cells that preferentially interact with iMSCs, potentially reinforcing local inflammation. These findings position iMSCs as central mediators of early BM niche dysfunction and potential therapeutic targets for intercepting pre-malignant hematopoiesis.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.