Abstract
Erythroblastic islands (EBIs), discovered more than 60 years ago, are specialized microenvironments for erythropoiesis. This island consists of a central macrophage with surrounding developing erythroid cells. EBI macrophages have received intense interest in the verifications of the supporting erythropoiesis hypothesis. Most of these investigations have focused on the identification and functional analyses of EBI macrophages, yielding significant progresses in identifying and isolating EBI macrophages, as well as verifying the potential roles of EBI macrophages in erythropoiesis. EBI macrophages express erythropoietin receptor (Epor) both in mouse and human, and Epo acts on both erythroid cells and EBI macrophages simultaneously in the niche, thereby promoting erythropoiesis. Impaired Epor signaling in splenic niche macrophages significantly inhibit the differentiation of stress erythroid progenitors. Moreover, accumulating evidence suggests that EBI macrophage dysfunction may lead to certain erythroid hematological disorders. In this review, the heterogeneity, identification, and functions of EBI macrophages during erythropoiesis under both steady-state and stress conditions are outlined. By reviewing the historical data, we discuss the influence of EBI macrophages on erythroid hematopoietic disorders and propose a new hypothesis that erythroid hematopoietic disorders are driven by EBI macrophages.
Highlights
“Erythropoiesis is a process by which hematopoietic stem cells (HSCs) proliferate and differentiate via multiple distinct developmental stages, to eventually generate mature red blood cells (RBCs)” (Yan et al, 2017; Huang et al, 2018; Qu et al, 2018)
The Erythroblastic islands (EBIs), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered by Marcel Bessis in (1958)
Flow cytometry and imagestream results revealed that Vcam1 and CD169 are broadly distributed on EBI macrophages, only a proportion of EBI macrophages express CD163 and Ly6C (Li et al, 2019) in mouse bone marrow (BM)
Summary
“Erythropoiesis is a process by which hematopoietic stem cells (HSCs) proliferate and differentiate via multiple distinct developmental stages, to eventually generate mature red blood cells (RBCs)” (Yan et al, 2017; Huang et al, 2018; Qu et al, 2018) This process occurs at the erythroblastic island (EBI), which is composed of a central macrophage surrounded by developing erythroid cells (BESSIS, 1958). An’s group used the Epor-eGFPcre mouse model and a specific antibody against human EPOR, to characterize EBI macrophages (Li et al, 2019) They performed RNA sequence of the newly identified Epor+ EBI macrophages to reveal specialized functions and potential molecular mechanisms of EBI macrophages in supporting erythropoiesis. We further highlight significant unanswered questions in view of providing vital knowledge to guide understanding of this tightly regulated process in normal and disordered erythropoiesis of hematologic diseases such as βthalassemia and polycythemia vera (PV), among others
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