Cross-Talk between Haematopoietic Cells and Stromal cells Subsets Drives the Remodelling of the Bone Marrow Microenvironment in Myeloproliferative Neoplasms

In a proportion of patients with myeloproliferative neoplasms (MPNs), severe remodelling of the bone marrow (BM) microenvironment develops, with myelofibrosis (MF) and osteosclerosis leading to cytopenias and poor survival. Mesenchymal stromal cells (MSC) have been implicated in MF pathogenesis (Leimkühler, Cell Stem Cell, 2021), including nestin+ (Arranz, Nature, 2014), Gli1+ (Schneider, Cell Stem Cell, 2017) and leptin-receptor+ MSCs (Decker, Nat Cell Bio, 2017). However, little is known about the cellular subtypes and transcriptional states of fibroblast subtypes in MF, and the key receptor-ligand (R-L) interactions that lead to their activation. Our aim was to build a fully comprehensive atlas of MF BM and clarify the pathological interactions between MPN cells and their stromal environment. We used 10x genomics platform to profile single-cell transcriptome of total momonuclear cells, hematopoietic stem/progenitor cells, CD41+ cells and stromal cells from the murine MPL W515L model of myelofibrosis