Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic Progenitors

Spleen and bone marrow (BM) have been shown to contain the progenitors of a novel dendritic-like antigen-presenting cell type (L-DC). These progenitors are also maintained in both long-term spleen cultures and co-cultures of spleen or BM over the stromal cell line STX3. We examined mouse foetal liver (FL), rich in hematopoietic stem/progenitor cells (HSC/HPC) after embryonic day (E) 12.5, for the presence of L-DC progenitors by testing their capacity to colonize STX3 and produce L-DC. E14.5 FL from wild-type C57BL/6J mice was found to colonize STX3 and produce L-DC for 28 days. By contrast, E14.5 FL from Ikaros Plastic mice gave only short-term production of low numbers of L-DC between 7 and 14 days of co-culture. The transient and weak production of L-DC by FL from Plastic E14.5 mice maps to the loss of self-renewal capacity amongst HSC. L-DC progenitors are, therefore, closely aligned with a subset of self-renewing HSC/HPC in FL.