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Blood. 2019 Aug 1;134(5):480-491. doi: 10.1182/blood.2019000430. Epub 2019 May 17.

Identification and transcriptome analysis of erythroblastic island macrophages.

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School of Life Sciences, Zhengzhou University, Zhengzhou, China.
Laboratory of Membrane Biology, New York Blood Center, New York, NY.
Department of Immunotherapy.
Department of Hematology, and.
Department of Lymphatic Internal Medicine, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY.
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Department of Pediatrics, Pathology and Genetics, Yale University School of Medicine, New Haven, CT.
Laboratory of Complement Biology, New York Blood Center, New York, NY; and.
Molecular Biology Research Center & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.


The erythroblastic island (EBI), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered. The identity of EBI macrophages has thus far remained elusive. Given that Epo is essential for erythropoiesis and that Epor is expressed in numerous nonerythroid cells, we hypothesized that EBI macrophages express Epor so that Epo can act on both erythroid cells and EBI macrophages simultaneously to ensure efficient erythropoiesis. To test this notion, we used Epor-eGFPcre knockin mouse model. We show that in bone marrow (BM) and fetal liver, a subset of macrophages express Epor-eGFP. Imaging flow cytometry analyses revealed that >90% of native EBIs comprised F4/80+Epor-eGFP+ macrophages. Human fetal liver EBIs also comprised EPOR+ macrophages. Gene expression profiles of BM F4/80+Epor-eGFP+ macrophages suggest a specialized function in supporting erythropoiesis. Molecules known to be important for EBI macrophage function such as Vcam1, CD169, Mertk, and Dnase2α were highly expressed in F4/80+Epor-eGFP+ macrophages compared with F4/80+Epor-eGFP- macrophages. Key molecules involved in iron recycling were also highly expressed in BM F4/80+Epor-eGFP+ macrophages, suggesting that EBI macrophages may provide an iron source for erythropoiesis within this niche. Thus, we have characterized EBI macrophages in mouse and man. Our findings provide important resources for future studies of EBI macrophage function during normal as well as disordered erythropoiesis in hematologic diseases such as thalassemia, polycythemia vera, and myelodysplastic syndromes.


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