粒细胞生成
红细胞生成
造血
骨髓
生物
促红细胞生成素
细胞生物学
免疫学
糖蛋白
转录组
干细胞
贫血
医学
抗原
遗传学
内科学
基因表达
基因
作者
Laurel Romano,Katie G. Seu,Julien Papoin,David E. Muench,Diamantis G. Konstantinidis,André Olsson,Katrina Schlum,Kashish Chetal,Joel Anne Chasis,Narla Mohandas,Betsy Barnes,Yi Zheng,H. Leighton Grimes,Nathan Salomonis,Lionel Blanc,Theodosia A. Kalfa
出处
期刊:Blood
[American Society of Hematology]
日期:2022-07-21
卷期号:140 (14): 1621-1634
被引量:18
标识
DOI:10.1182/blood.2022015724
摘要
Abstract The erythroblastic island (EBI), composed of a central macrophage surrounded by maturing erythroblasts, is the erythroid precursor niche. Despite numerous studies, its precise composition is still unclear. Using multispectral imaging flow cytometry, in vitro island reconstitution, and single-cell RNA sequencing of adult mouse bone marrow (BM) EBI-component cells enriched by gradient sedimentation, we present evidence that the CD11b+ cells present in the EBIs are neutrophil precursors specifically associated with BM EBI macrophages, indicating that erythro-(myelo)-blastic islands are a site for terminal granulopoiesis and erythropoiesis. We further demonstrate that the balance between these dominant and terminal differentiation programs is dynamically regulated within this BM niche by pathophysiological states that favor granulopoiesis during anemia of inflammation and favor erythropoiesis after erythropoietin stimulation. Finally, by molecular profiling, we reveal the heterogeneity of EBI macrophages by cellular indexing of transcriptome and epitope sequencing of mouse BM EBIs at baseline and after erythropoietin stimulation in vivo and provide a searchable online viewer of these data characterizing the macrophage subsets serving as hematopoietic niches. Taken together, our findings demonstrate that EBIs serve a dual role as niches for terminal erythropoiesis and granulopoiesis and the central macrophages adapt to optimize production of red blood cells or neutrophils.
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