摘要：SummaryThe cardinal property of bone marrow (BM) stromal cells is their capacity to contribute to hematopoietic stem cell (HSC) niches by providing mediators assisting HSC functions. In this study we first contrasted transcriptomes of stromal cells at different developmental stages and then included large number of HSC-supportive and non-supportive samples. Application of a combination of algorithms, comprising one identifying reliable paths and potential causative relationships in complex systems, revealed gene networks characteristic of the BM stromal HSC-supportive capacity and of defined niche populations of perivascular cells, osteoblasts, and mesenchymal stromal cells. Inclusion of single-cell transcriptomes enabled establishing for the perivascular cell subset a partially oriented graph of direct gene-to-gene interactions. As proof of concept we showed that R-spondin-2, expressed by the perivascular subset, synergized with Kit ligand to amplifyex vivohematopoietic precursors. This study by identifying classifiers and hubs constitutes a resource to unravel candidate BM stromal mediators.Graphical AbstractDisplay OmittedHighlights•A correlation network with predictor genes for the BM HSPC-supportive stromal niche•An information theoretic network for the supportive perivascular stromal niche•Wnt facilitator Rspo2 together with SCF to amplifyex vivohematopoietic precursors•Resource combining bioinformatics algorithms to search for novel stromal mediatorsCell Biology; Stem Cells Research; Bioinformatics
