Lastly, a shout-out to Marc Raaijmakers’ team at
@erasmusmc.bsky.social 🎉📢 whose complementary work led by Lanpeng Chen and Yujie Bian revealed similar inflammatory bone marrow remodeling in MDS and made a link to leukemic evolution. A story that unfolded in parallel! ✏️
shorturl.at/4G8Yr

Huge thanks to my fellow co–first authors Kevin and Maksim: together we pushed this project forward. 💪 Grateful to Judith and Borhane for support 🙏 and all collaborators @embl.org @biomedizin.unibas.ch @unimainz.bsky.social @tudresden.bsky.social @dkfz.bsky.social @trowbridgelab.bsky.social @ki.se

🎯 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.

Together with collaborators from @ki.se, we developed and applied SpliceUp, a pipeline for detecting aberrant splicing from scRNA-seq (shorturl.at/d8Evh), and could detect splice factor (SF3B1) mutated MDS cells. We showed that these mutated HSPCs in MDS are not directly driving inflammation.

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! 🦴🩸🧬🔬

Huge thanks to my fellow co–first authors Kevin and Maksim: together we pushed this project forward. 💪 Grateful to Judith and Borhane for support 🙏 and all collaborators @embl.org @biomedizin.unibas.ch
@unimainz.bsky.social @tudresden.bsky.social @dkfz.bsky.social @trowbridgelab.bsky.social @ki.se

🎯 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.

Together with collaborators from @ki.se, we developed and applied SpliceUp, a pipeline for detecting aberrant splicing from scRNA-seq (shorturl.at/d8Evh), and could detect splice factor (SF3B1) mutated MDS cells. We showed that these mutated HSPCs in MDS are not directly driving inflammation.

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! 🦴🩸🧬🔬

As we wait for the final version in the journal, I leave here the last version that we uploaded on bioarchive.
I hope you like it!

www.biorxiv.org/content/10.1...