Roles of spleen and liver in development of the murine hematopoietic system

Objective Hematopoietic stem cells (HSCs) and colony-forming progenitor cells (CFCs) are believed to migrate from liver to bone marrow (BM) around the time of birth, where they remain throughout the animalʹs life. Although in mice the spleen is also a hematopoietic organ, neither the origin nor the contribution of spleen HSCs to hematopoietic homeostasis has been assessed relative to that of BM HSCs. To investigate these issues we quantitated CFC and HSC activity in the spleen, BM, peripheral blood, and liver of the mouse during ontogeny. Methods CFCs were assessed by clonogenic colony formation, and HSCs by long-term reconstituting ability. Results CFCs gradually increased in the BM and decreased in the liver with age. Increased prevalence of CFCs in fetal and pup blood occurred at day (d) 12 postcoitus (pc) and during the period of d16 pc to 4d postbirth, corresponding to the times when hematopoietic cells migrate from the yolk sac and/or aorta-gonad-mesonephros (AGM) to the fetal liver and from the neonatal liver to the BM, respectively. In the spleen, CFCs displayed two peaks of activity at 2d and 14d–15d postbirth. Spleen HSCs also fluctuated during this time period. Neonatal splenectomy did not alter CFC or HSC frequencies in the BM, but CFCs increased in the livers of splenectomized mice. Conclusion These data demonstrate that the liver may act as a site of extramedullary hematopoiesis in the neonate, especially in the absence of the spleen, and imply that the spleen, BM, and liver cooperatively contribute to hematopoietic homeostasis.