Stress erythropoiesis in atherogenic mice

Ángela Sánchez,Marta C. Orizaola,Diego Rodríguez-Muñoz,Antonio Castrillo,Ana Aranda,Susana Alemany

doi:10.1038/s41598-020-74665-x

Abstract

Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen. Here, we show an increase in the number of circulating erythrocytes in apolipoprotein E−/− mice fed a Western high-fat diet, with similar number of circulating leukocytes and CD41+ events (platelets). Atherogenic conditions increase spleen erythropoiesis with no variations of this cell lineage in the bone marrow. Spleens from atherogenic mice show augmented number of late-stage erythroblasts and biased differentiation of progenitor cells towards the erythroid cell lineage, with an increase of CD71+CD41CD34−CD117+Sca1−Lin− cells (erythroid-primed megakaryocyte-erythroid progenitors), which is consistent with the way in which atherogenesis modifies the expression of pro-erythroid and pro-megakaryocytic genes in megakaryocyte-erythroid progenitors. These data explain the transiently improved response to an acute severe hemolytic anemia insult found in atherogenic mice in comparison to control mice, as well as the higher burst-forming unit-erythroid and colony forming unit-erythroid capacity of splenocytes from atherogenic mice. In conclusion, our work demonstrates that, along with the well stablished enhancement of monocytosis during atherogenesis, stress erythropoiesis in apolipoprotein E−/− mice fed a Western high fat diet results in increased numbers of circulating red blood cells.

Highlights

Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen
multipotent progenitor populations (MPPs) are responsible for homeostatic hematopoiesis and together with hematopoietic stem cells (HSC) are included in the so-called hematopoietic stem progenitor cell population (HSPC)
They lack expression of CD38, which is upregulated in the lineage-restricted cell progenitors, which include the progenitors for all major branches of hematopoiesis: the common myeloid progenitors (CMPs) and the common lymphoid progenitors (CLPs)

Summary

Introduction

Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen. Under conditions of severe hypoxia, caused by hemorrhage or BM suppression secondary to chemotherapy, there is an enormous response of the splenic stress erythropoiesis to rapidly restore the oxygen supply to tissues This alternative stress erythropoietic pathway amplifies specific erythroid-restricted self-renewing cell progenitors in the spleen through the signalling. The BM cell differentiation is rapidly biased towards the myeloid branch in detriment of erythropoiesis[18,19] along with increased levels of erythroblast apoptosis and the subsequent clearance of the apoptotic corpses (erythrophagocytosis)[20,21,22,23] This decrease in the input of mature RBC generated in BM is compensated by splenic stress erythropoiesis (reviewed in23,24). In chronic inflammatory diseases the strategy to mitigate inflammatory anemia is the periodic increase of stress erythropoiesis in s pleen[24,25,26]

Methods

Results

Conclusion