🎯 Inflammation and niche remodelling are hallmarks in both CHIP to MDS, underscoring the role of the microenvironment in early myeloid disease. Targeting this stromal-immune remodelling could open new interception strategies.

In co-culture experiments 🧫, we showed that healthy & CHIP HSPCs engaged with stromal cells to receive support 🩸🫂(e.g., CXCL12), but MDS HSPCs failed to do so. MDS blasts (!) even triggered an inflammatory program in stromal cells.

On the immune side 🧪: we found IFN-responsive T cells enriched in MDS that preferentially interact with iMSCs, hinting at a stromal-immune axis of bone marrow niche inflammation. An inflammatory feedback loop?

Key finding: we identified a novel population of “inflammatory mesenchymal stromal cells” (iMSCs) that appear in asymptomatic and already low-VAF CHIP and expand further in MDS, while healthy CXCL12+ adipogenic stromal cells decline in the bone marrow. 🧬🔬

We studied human bone marrow samples from 84 donors (age-matched healthy controls, CHIP carriers, and early MDS patients) using single-cell RNA-seq, imaging, flow cytometry, and functional co-culture assays. 🧫

The scale of human stromal niche profiling is what makes this study special! 🦴🩸🧬🔬

🎯 Inflammation and niche remodelling are hallmarks in both CHIP to MDS, underscoring the role of the microenvironment in early myeloid disease. Targeting this stromal-immune remodelling could open new interception strategies.

In co-culture experiments 🧫, we showed that healthy & CHIP HSPCs engaged with stromal cells to receive support 🩸🫂(e.g., CXCL12), but MDS HSPCs failed to do so. MDS blasts (!) even triggered an inflammatory program in stromal cells.

On the immune side 🧪: we found IFN-responsive T cells enriched in MDS that preferentially interact with iMSCs, hinting at a stromal-immune axis of bone marrow niche inflammation. An inflammatory feedback loop?

Key finding: we identified a novel population of “inflammatory mesenchymal stromal cells” (iMSCs) that appear in asymptomatic and already low-VAF CHIP and expand further in MDS, while healthy CXCL12+ adipogenic stromal cells decline in the bone marrow. 🧬🔬

We studied human bone marrow samples from 84 donors (age-matched healthy controls, CHIP carriers, and early MDS patients) using single-cell RNA-seq, imaging, flow cytometry, and functional co-culture assays. 🧫

The scale of human stromal niche profiling is what makes this study special! 🦴🩸🧬🔬