Cell-cell interactome of the hematopoietic niche and its changes in acute myeloid leukemia
Sarah Ennis, Alessandra Jordano Conforte, Eimear O’Reilly, Javid Sabour Takanlu, Tatiana Cichocka, Sukhraj Pal Singh Dhami, Pamela Nicholson, Philippe Krebs, Pilib Ó Broin, Éva Szegezdi
Abstract
The bone marrow (BM) is a complex microenvironment, coordinating the production of billions of blood cells every day. Despite its essential role and its relevance to hematopoietic diseases, this environment remains poorly characterized. Here we present a high-resolution characterization of the niche in health and acute myeloid leukemia (AML) by establishing a single-cell gene expression database of 339,381 BM cells. We found significant changes in cell type proportions and gene expression in AML, indicating that the entire niche is disrupted. We then predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other BM cell types, revealing a remarkable expansion of predicted interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. In particular, predicted interactions involving transforming growth factor β1 (TGFB1) become widespread, and we show that this can drive AML cell quiescence in vitro . Our results highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment, fostering AML growth.