Roundabout ways to lineage commitment

Abstract

The lineage potential, heterogeneity, and relationships of hematopoietic stem and progenitor cells (HSPCs) are currently unclear. To gain new insights into these questions, we performed quantitative analyses of mature cell production by transplanted HSPCs. Assessment of the absolute numbers of mature cell types produced by each progenitor cell revealed a striking erythroid bias of all myeloid-competent progenitors assessed, accompanied by strong platelet production that far exceeded generation of myelomonocytic, B and T cells. Clonal analysis by single cell transplantation and spleen colony assays revealed that a significant fraction of HSCs and multipotent progenitors have multilineage potential at the single-cell level. The physiological relevance of this multipotency was underscored by lineage tracing analysis that demonstrated that all hematopoietic lineages develop through a shared stage in situ. Collectively, these new insights prompt an erythroid-biased model of hematopoietic differentiation. We acknowledge funding from NHLBI, NIDDK, NIAID, the American Cancer Society and the American Asthma Foundation.