GSE196347
Erythroblastic islands foster granulopoiesis in parallel to terminal erythropoiesis
The erythroblastic island (EBI), composed of a central macrophage and surrounding maturing erythroblasts, is the erythroid precursor niche.  Despite numerous studies, its precise composition is still unclear. Using multispectral imaging flow cytometry (IFC), in vitro island reconstitution, and single cell RNA-seq of EBI-component cells enriched by gradient sedimentation, we present evidence that CD11b+ cells present in the EBIs are neutrophil precursors specifically associated with bone marrow EBI macrophages, indicating that erythro-(myelo)-blastic islands are a site for terminal granulopoiesis as well as erythropoiesis and production of these lineages is dynamically regulated within this niche.  We further demonstrate that the balance between these lineages is determined by pathophysiological conditions, favoring granulopoiesis during anemia of inflammation, or erythropoiesis after erythropoietin (Epo) stimulation.  Finally, we provide the heterogeneous molecular profiling of EBI macrophages as revealed by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo.  Altogether, these data demonstrate that EBIs serve a dual role as terminal erythropoiesis and granulopoiesis niches and the central macrophages adapt to the needs of stress erythropoiesis as well as granulopoiesis. Overall design: Single-cell RNA-Seq and CITE-Seq of murine erythroblastic islands