TY - JOUR
T1 - Identification and transcriptome analysis of erythroblastic island macrophages
AU - Li, Wei
AU - Wang, Yaomei
AU - Zhao, Huizhi
AU - Zhang, Huan
AU - Xu, Yuanlin
AU - Wang, Shihui
AU - Guo, Xinhua
AU - Huang, Yumin
AU - Zhang, Shijie
AU - Han, Yongshuai
AU - Wu, Xianfang
AU - Rice, Charles M.
AU - Huang, Gang
AU - Gallagher, Patrick G.
AU - Mendelson, Avital
AU - Yazdanbakhsh, Karina
AU - Liu, Jing
AU - Chen, Lixiang
AU - An, Xiuli
N1 - Publisher Copyright:
© 2019 American Society of Hematology. All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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 F4/801Epor-eGFP1 macrophages. Human fetal liver EBIs also comprised EPOR1 macrophages. Gene expression profiles of BM F4/801Epor-eGFP1 macrophages suggest a specialized function in supporting erythropoiesis. Molecules known to be important for EBI macrophage function such as Vcam1, CD169, Mertk, and Dnase2a were highly expressed in F4/801Epor-eGFP1 macrophages compared with F4/801Epor-eGFP2 macrophages. Key molecules involved in iron recycling were also highly expressed in BM F4/801Epor-eGFP1 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.
AB - 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 F4/801Epor-eGFP1 macrophages. Human fetal liver EBIs also comprised EPOR1 macrophages. Gene expression profiles of BM F4/801Epor-eGFP1 macrophages suggest a specialized function in supporting erythropoiesis. Molecules known to be important for EBI macrophage function such as Vcam1, CD169, Mertk, and Dnase2a were highly expressed in F4/801Epor-eGFP1 macrophages compared with F4/801Epor-eGFP2 macrophages. Key molecules involved in iron recycling were also highly expressed in BM F4/801Epor-eGFP1 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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U2 - 10.1182/blood.2019000430
DO - 10.1182/blood.2019000430
M3 - Article
C2 - 31101625
AN - SCOPUS:85070588387
SN - 0006-4971
VL - 134
SP - 480
EP - 491
JO - Blood
JF - Blood
IS - 5
ER -