Cell-cell interactome of the hematopoietic niche and its changes in acute myeloid leukemia

The bone marrow (BM) is a complex microenvironment, coordinating the produc-tion 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 data-base 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 b1 (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.

Automated summary

In this study, a single-cell gene expression database of 339,381 bone marrow cells was established to comprehensively characterize the microenvironment of both healthy and acute myeloid leukemia (AML). Significant changes in cell type proportions and gene expression were observed in AML, indicating disruption of the entire niche. Predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other bone marrow cell types were also explored, revealing an expansion of interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. Transforming growth factor b1 (TGFB1)-related interactions were particularly widespread and were shown to drive AML cell quiescence in vitro. These findings highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment fostering AML growth.