Lineage commitment of hematopoietic stem cells and progenitors: insights from recent single cell and lineage tracing technologies

Abstract

Blood production is essential to maintain human health, and even small perturbations in hematopoiesis can cause disease. Hematopoiesis has therefore been the focus of much research for many years. Experiments determining the lineage potentials of hematopoietic stem and progenitor cells (HSPCs) in vitro and after transplantation revealed a hierarchy of progenitor cell states, where differentiating cells undergo lineage commitment-a series of irreversible changes that progressively restrict their potential. New technologies have recently been developed that allow for a more detailed analysis of the molecular states and fates of differentiating HSPCs. Proteomic and lineage-tracing approaches, alongside single-cell transcriptomic analyses, have recently helped to reveal the biological complexity underlying lineage commitment during hematopoiesis. Recent insights from these new technologies were presented by Dr. Marjorie Brand and Dr. Allon Klein in the Summer 2019 ISEH Webinar, and are discussed in this Perspective.

Figure 1:. Models of hematopoietic stem cell lineage commitment.

(A) The classical hematopoietic tree model, which suggested lineage commitment associated with branching transitions between cells with distinct lineage potentials. (B) A schematic representation of hematopoiesis based on recent findings discussed within the review, which suggest that HSC differentiation occurs via continuum with phenotypically defined progenitor populations representing heterogeneous lineage potential. (C) Lineage tracing in combination with single cell analyses have suggested that (1) the predominant fate of HSCs in native hematopoiesis is megakaryopoiesis and (2) there may be multiple lineage trajectories that generate equivalent mature hematopoietic cell types. For example, monocytes may be generated via dendritic (DC)-like or neutrophil-like trajectories.