We hope this work opens new possibilities for targeted therapies in MM. There is a lot of biological validation that needs to be done using these scRNAseq data as a blueprint. More to come! #plasmacell #mmsm

To investigate EndMT features, we tested JQ1, a BET inhibitor known to affect mesenchymal features. However, JQ1 didn’t reverse mesenchymal markers in MM ECs, suggesting that MM ECs may require different, more complex intervention strategies. @JunQiLab

Interestingly, while VEGF inhibitors haven’t shown success in MM, our findings suggest that targeting alternative pathways, such as PDGFA, could disrupt the supportive role of ECs in MM. This needs to be tested in vitro and in vivo before we jump into conclusions!

Fascinatingly, MM ECs are highly interactive within the bone marrow. We found enhanced cell–cell signaling, particularly between ECs and mesenchymal stem cells (MSCs), which likely reinforce MM cell survival and growth.

To dive deeper, we developed a new protocol to isolate & culture ECs from MM patients' bone marrow, allowing us to study these cells’ pro-tumor activities in vitro. This model opens avenues for testing therapies directly on MM-derived ECs!

We observed upregulation of genes like VIM, CTNNB1, and SMAD3 in MM ECs, associated with a shift towards a mesenchymal-like state. This suggests that MM ECs undergo an endothelial-to-mesenchymal transition (EndMT), which may aid MM cell invasion and angiogenesis.

Madelon's paper: nature.com/articles/s41...
Thanks for the huge help without which this analysis would not be possible!

Using data from @NatImmunol paper by @mdejong.bsky.social et al. we identified unique pathway activations in MM-derived ECs, setting them apart from healthy controls. Key pathways? Epithelial–mesenchymal plasticity (EMP) and TGF-beta. MM microenvironemnt seems very complex #scRNAseq

Link: mdpi.com/1422-0067/25...
Thread below.