Instructive interaction between myelodysplastic hematopoiesis and the bone marrow microenvironment at the single-cell level

• DOI: 10.1016/j.bneo.2024.100021
• Publication Date: 2024-05-21T04:09:52Z
• Authors: Johann-Christoph ...; Nanni Schmitt; Alexander Streuer; Qingyu Xu; Vladimir Riabov; Eva Altrock; Nadine Weimer; Verena Nowak; Julia Obländer; Iris Palme; Melda Göl; Marie Demmerle; Felicitas Rapp; Fabian Siegel; Laurenz Steiner; Mahmoud Ghazal; Angelika Duda; Verena Haselmann; Ali Darwich; Ahmed Jawhar; Mohamad Jawhar; Georgia Metzgeroth; Wolf-Karsten Hofmann; Daniel Nowak

Myelodysplastic Neoplasms (MDS) are hypothesized to re-model their bone marrow (BM) microenvironment reinforce conditions for propagation. In this study, we investigated interactions between MDS cells and the BM niche at single cell level. a patient-derived xenograft (PDX) model, analyzed 13,000 of different murine populations after long-term (>24 weeks) exposure versus healthy human grafts. Subsequently, over 24,000 primary enriched non-hematopoietic compartment by using whole fragments from n=8 patients n=7 age-matched donors. transplanted PDX, mesenchymal (MSC) subpopulations were forced overexpress hematopoietic factors such as Cxcl12 Il7 upon contact with compared Single analyses in situ showed highly heterogeneous MSC on patient-individual We identified inflammatory gene expression profiles well overexpression CXCL12, KITLG IL7 MSCs endothelial cells. conclusion, demonstrate re-programming pointing altered increased growth factor subgroup patients.