Abstract
The 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 enabled identifying a gene network characteristic of the BM stromal HSC-supportive capacity and defining 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 amplify ex vivo hematopoietic precursors. Our strategy, first defining the gene organization underlying a functional phenotype then identifying the cell sets contributing to that phenotype, may be generalized to any transcriptome analysis.
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