Integrated Calendar

Hematopoietic stem cells (HSCs) and their subsequent progenitors produce blood cells, but the precise nature of this production is dogged by controversy. Cellular barcoding is a powerful experimental technique that simultaneously traces the in vivo differentiation of individual cells. Using cellular barcoding, we traced the progeny of hematopoietic progenitors and reconstituted the lineage relationship with single cell resolution. We show that individual multipotent progenitors are generally not multi-outcome; instead, they produce heterogeneous patterns of limited types of blood cells. Interestingly, we found that some progenitors produce dendritic cells without producing any lymphoid and myeloid cells, redefining dendritic cells as a third lineage of blood cells. We then developed a quantitative framework to infer the nature of the hematopoietic tree. With this approach, we showed that the classical model of hematopoiesis cannot explain our data and we propose an alternative model.