Transcriptional Characterization of the Stromal and Endothelial Bone Marrow Microenvironment during Progression from MGUS to Multiple Myeloma
Despite therapeutic advancements, Multiple Myeloma (MM) remains an incurable disease. To characterize the role that deregulation of the Bone Marrow (BM) microenvironment may have in the transition from healthy to Monoclonal Gammopathy of Undetermined Significance (MGUS), and from MGUS to MM, we performed single-cell RNA sequencing (scRNA-seq) of mesenchymal stromal cells (MSC) and endothelial cells (EC) from two mouse models, BIcgamma and MIcgamma, that recapitulate the principal clinical, genetic, and immunological characteristics of MGUS and MM patients. Our results identify distinct transcriptional dynamics between MSC and EC. While EC acquires a stress state during MGUS, a proliferating and angiogenic profile characterizes MM. On the other hand, MSC compromised their differentiation potential, exhibiting a more inflammatory profile that initiates from the MGUS stage. Interestingly, we identified interferon (IFN)-related myeloma signature in malignant EC of the BIcgamma model, which