Monocyte-derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia

Chang Liao, K. Sandeep Prabhu and Robert F. Paulson

Key Points

  • During the recovery from anemia, monocytes recruited to the spleen generate macrophages that form the stress erythropoiesis niche.

  • The maturation of monocytes into macrophages occurs in parallel with stress erythroid progenitor development.

Publisher's Note: There is a Blood Commentary on this article in this issue.


Anemic stress induces a physiological response that includes the rapid production of new erythrocytes. This process is referred to as stress erythropoiesis. It is best understood in the mouse where it is extramedullary and utilizes signals and progenitor cells that are distinct from bone marrow steady-state erythropoiesis. The development of stress erythroid progenitors occurs in close association with the splenic stress erythropoiesis niche. In particular, macrophages in the niche are required for proper stress erythropoiesis. Here we show that the expansion of the niche occurs in concert with the proliferation and differentiation of stress erythroid progenitors. Using lineage tracing analysis in 2 models of anemic stress, we show that the expansion of the splenic niche is due to the recruitment of monocytes into the spleen, which develop into macrophages that form erythroblastic islands. The influx in monocytes into the spleen depends in part on Ccr2-dependent signaling mediated by Ccl2 and other ligands expressed by spleen resident red pulp macrophages. Overall, these data demonstrate the dynamic nature of the spleen niche, which rapidly expands in concert with the stress erythroid progenitors to coordinate the production of new erythrocytes in response to anemic stress.

  • Submitted June 7, 2018.
  • Accepted September 27, 2018.
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