Hematopoietic Stem Cells in Health and Disease-Insights from Single-Cell Multi-omic Approaches

Purpose of Review Hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells. This review provides an overview of how single-cell (multi)-omic approaches have recently advanced our understanding of healthy hematopoiesis, hematological malignancies, and the stem cell niche. Recent Findings Single-cell technologies have revealed tremendous heterogeneity of the HSC compartment, conflicting with the classical view of hematopoiesis. Large-scale single-cell approaches mapping the entire hematopoietic system have enabled an ordering of the observed heterogeneity along meaningful differentiation and cell-state trajectories. These studies provided novel insights into lineage commitment pathways and led to the suggestion of advanced models of hematopoiesis. Single-cell multi-omic technologies, where several entities of individual cells are measured in parallel, have permitted the fine mapping of clonal and developmental differentiation hierarchies, and revealed the molecular consequences of clonal diversification. Recent single-cell approaches have changed our perception of healthy hematopoiesis, provided an understanding of hematological malignancies at unprecedented depth, and revealed new insights into the stem cell niche.