Transcriptomic characterisation of haematopoietic stem and progenitor cells from adult human homeostatic (non-mobilised) peripheral blood

Haematopoietic stem and progenitor cells (HSPCs), the precursors of all blood cells, reside predominantly in the bone marrow. Yet, a small proportion (<1%) of phenotypic HSPCs circulates through peripheral blood (PB) at any given time. To date, the detailed characterization of steady-state circulating HSPCs in adult humans remains very poor. Here, we analyse the single-cell composition of the adult human HSPC pool within non-mobilised PB from four healthy donors. 10x scRNA-seq of 51,000 HSPCs from all six donors was paired with single-cell functional analysis using most immature haematopoietic stem cells and multipotent progenitors (HSC/MPPs). We find that long-term functional HSC/MPPs are very rare in non-mobilised PB, and that a large fraction of circulating HSPCs is biased towards the erythroid lineage. In particular, we detect the enrichment of a subset of exclusively erythroid/megakaryocyte-primed quiescent HSC-like cells within the phenotypic PB HSC/MPP compartment.