ENAGenomicsComputational Biology and Bionformatics, Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA238542Homo sapiensWe used collection of sequentially mutated BM-hMSCs ranging from wild type (no oncogenic hits) to fully transformed hMSCs (targeted with up six oncogenic mutations)to address whether BM-hMSCs at different stages of a well-characterized oncogenic process (normal, immortalized, transformed) retain immunomodulatory properties in vitro and in vivo. We characterize, for the first time, an oncogenic transformation-associated loss of the immunesuppressive and anti-inflammatory properties by hMSCs and identify candidate immune effectors underlying the loss of immunomodulation in transformed hMSCs. Overall design: Wild type BM-hMSCs (MSC-0H-GFP) did not develop tumors, meanwhile hMSCs transformed sequentially transformed with 5 oncogenic lesions (p53 inactivation Rb inactivation expression of hTERT stabilization of c-myc and expression of oncogenic H-RAS) (MSC-5H-GFP) cells gave rise to undifferentiated sarcomas when inoculated into immunedeficient mice. The tumoral transformation process causes the loss of the immunosuppressive and anti-inflamatory propierties of MSC-5H-GFP cells as compared to those of the wild type MSC-0H-GFP cells. To understand the basis of this loss of immunosuppression in transformed hMSCs, gene expression analysis was performed to create the list of differentially expressed genes between MSC-0H-GFP and MSC-5H-GFP cells. Further analysis of altered signaling pathways and upstream regulators were performed using the Ingenuity Pathway Analysis software.xref:PubMed:25358789ENAfalseHomo sapiensLoss of immunosuppressive and anti-inflammatory properties in transformed human mesenchymal stem cells2025-09-242015-05-20PRJNA238542GSE55108960625358789