GSE107490 TGF β1-mediated functional inhibition of mesenchymal stromal cells in MDS and AML

Contributors : Stefanie Gey ; Manuel Rodr íguez-Paredes ; Paul Jäger ; Annemarie Koch ; Felix Bormann ; Julian Gutekunst ; Christoph Zilkens ; Ulrich Germing ; Guido Kobbe ; Frank Lyko ; Rainer Haas ; Thomas SchroederSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMesenchymal stromal cells (MSC) are involved in the pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but how they contribute to the expansion of malignant cells and hematopoietic failure is poorly understood. To further characterize the pathological phenotype we performed RNA sequencing of MSC from patients with MDS and AML. Data analysis revealed a specific molecular signature with a significant overlap of genes commonly deregulated in all MDS subtypes and in AML. Pathway analysis revealed a strong enrichment of genes related to osteogenesis, senescence, inflammatory processes and inhibitory cytokines thereby reflecting the structural and functional deficits of MDS- and AML-derived MSC on a molecular level. Further analysis identified TGF ß1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to TGFß1 healthy MSC adopted a phenotype reminiscent of that observed in primary patient-derived MSC which was characterized by impaired growth potential, osteogenic differentiation capacities, a specific gene expression profile and diminished stromal hematopoietic support. These suppressive ef...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research