mRNA profiles of bone marrow and splenic hematopoietic stem cells after 5-FU challenge
Under stress hematopoiesis, previous studies have suggested the migration of hematopoietic stem cells (HSCs) from bone marrow (BM) to extramedullary sites such as spleen. However, there is little direct evidence of HSC migration from BM to spleen. Here, we induced myeloablation via 5-fluorouracil (5-FU) and showed the direct evidence of HSC migration from BM to spleen during hematopoietic regeneration via a photoconvertible fluorophore. We found that during hematopoietic regeneration, there were mechanistic differences for HSC migration during early (day 3 to 8) and late phase (day 11 to 14). During steady-state, HSCs preferentially migrated to BM rather than spleen, but during the early phase HSC migration to spleen predominated. Indeed, in the early phase, HSC mobilization from BM was induced in G-CSF-dependent manners, while HSCs in the late phase gained significantly enhanced cell-autonomous motility, which was independent of chemotaxis. Collectively, HSC migration was dynamically changed during hematopoietic regeneration. Overall design: To investigate the transcriptional differences in bone marrow versus splenic hematopoietic stem cells after administration of the chemotherapeutic agent 5-fluorouracil (5-FU), we performed gene expression profiling. Mice were 8-12 weeks at the time of cell isolation