The Regulation of Hematopoietic Stem Cells and Erythropoiesis

Hematopoietic stresses mobilize hematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary hematopoiesis (EMH), including erythropoiesis. We assessed the sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by cyclophosphamide plus granulocyte colony-stimulating factor, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells (Nature 527:466, 2015). EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing their proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow hematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse hematopoietic stresses.During pregnancy, the blood volume increases relatively quickly, requiring increased erythropoiesis to maintain red blood cell counts. We discovered that HSCs in female mice divide significantly more frequently than in males as a result of estrogen/estrogen receptor signaling in HSCs (Nature 505:555). Estrogen levels increase during pregnancy, in...

Source: Blood - November 21, 2018 Category: Hematology Authors: Morrison, S. Tags: Blood Building: How to Make a Red Cell Source Type: research