Recent single cell tracking studies demonstrate a great deal of fate heterogeneity within the haematopoietic stem and progenitor cell population under steady-state conditions. However, the regulatory mechanisms of single cell fate during emergency conditions such as infection or cytokine exposure (where specific cell types increase in number) are largely unknown. This can theoretically occur either through greater clonal expansion of pre-existing progenitors, and/or emergency recruitment of progenitors. The latter might occur at the expense of other lineages through ‘lineage diversion’ or via recruitment of otherwise dormant progenitors.

To understand which of these scenarios accounts for fate commitment during an emergency Fms-like tyrosine kinase 3 ligand (FL) –mediated increase in dendritic cell (DC) numbers, we tagged individual progenitors with unique and heritable DNA barcodes and tracked their fate in vivo under steady-state and emergency conditions.

Our results indicated that diverse mechanisms accounted for the increased production of different DC subtypes (cDC1, cDC2 and pDC). For example, there was enhanced recruitment of cDC1-producing clones whereas the number of clones producing cDC2s and pDCs remained unchanged. In addition, increased clonal expansion was observed in almost all cDC1-contributing clones, while only subsets of cDC2 and pDC clones had larger clonal burst. Most interesting was a marked reduction of B cell-only clones concomitant with an increase in DC-only and DC & B cell-producing clones. This is consistent with lineage diversion of lymphoid-primed progenitors to produce DCs during FL stimulation.  The results highlight the intricacies of how individual progenitors modify their behaviour during demand-adapted haematopoiesis.