Integrated OMICs unveil the bone-marrow microenvironment in human leukemiaMore about Open Access at the Crick
Authors listDiana Passaro Manuel Garcia Albornoz Giovanni Diana Probir Chakravarty Linda Ariza-Mcnaughton Antoniana Batsivari Clara Borràs-Eroles Ander Abarrategi Alexander Waclawiczek Luigi Ombrato Ilaria Malanchi John Gribben Dominique Bonnet
The bone-marrow (BM) niche is the spatial environment composed by a network of multiple stromal components regulating adult hematopoiesis. We use multi-omics and computational tools to analyze multiple BM environmental compartments and decipher their mutual interactions in the context of acute myeloid leukemia (AML) xenografts. Under homeostatic conditions, we find a considerable overlap between niche populations identified using current markers. Our analysis defines eight functional clusters of genes informing on the cellular identity and function of the different subpopulations and pointing at specific stromal interrelationships. We describe how these transcriptomic profiles change during human AML development and, by using a proximity-based molecular approach, we identify early disease onset deregulated genes in the mesenchymal compartment. Finally, we analyze the BM proteomic secretome in the presence of AML and integrate it with the transcriptome to predict signaling nodes involved in niche alteration in AML.
Journal Cell Reports
Issue number 6