title: Intracellular reactive oxygen species mark and influence the megakaryocyte-erythrocyte progenitor fate of common myeloid progenitors.
abstract: While most studies regarding reactive oxygen species (ROS) focus on their deleterious biological effects, a growing body of evidence indicates the importance of ROS as critical mediators of several signaling pathways, including those involved in hematopoiesis. In this study, we show the critical role of ROS in lineage decision of myeloid progenitors. In megakaryocyte-erythrocyte progenitor cells (MEP), intracellular ROS levels were found to be as low as those in hematopoietic stem cells (HSC). In contrast, remarkably high intracellular ROS levels were observed in granulocyte-monocyte progenitor cells. Intracellular ROS levels in common myeloid progenitors (CMP) were inversely correlated with their MEP differentiation potential. Moreover, gene set enrichment analysis revealed that ROS-low CMP showed gene expression patterns similar to those of MEP, indicating that intracellular ROS levels mark the fate of CMP. In in vitro assays, ROS significantly suppressed the generation of MEP and the formation of megakaryocyte-erythrocyte colonies from CMP. In ROS-high CMP, expression of colony-stimulating factor one receptor (CSF1R) was highly upregulated, and its surface expression correlated with their granulocyte-monocyte differentiation potential. Furthermore, ROS was found to induce the expression of CSF1R mRNA in a leukemia cell line. These data provide novel insights into the relationship between ROS and the hematopoietic differentiation system.
authors.affiliation: Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Shinohara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Imai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Motoshi
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D022423:Myeloid Cells / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Biomarkers; Cell differentiation; Hematopoietic progenitor cells; Reactive oxygen species