title: A late-lineage murine neutrophil precursor population exhibits dynamic changes during demand-adapted granulopoiesis.
abstract: Homeostasis of neutrophils-the blood cells that respond first to infection and tissue injury-is critical for the regulation of immune responses and regulated through granulopoiesis, a multi-stage process by which neutrophils differentiate from hematopoietic stem cells. Granulopoiesis is a highly dynamic process and altered in certain clinical conditions, such as pathologic and iatrogenic neutropenia, described as demand-adapted granulopoiesis. The regulation of granulopoiesis under stress is not completely understood because studies of granulopoiesis dynamics have been hampered by technical limitations in defining neutrophil precursors. Here, we define a population of neutrophil precursor cells in the bone marrow with unprecedented purity, characterized by the lineage-CD11b+Ly6GloLy6BintCD115-, which we call NeuPs (Neutrophil Precursors). We demonstrated that NeuPs differentiate into mature and functional neutrophils both in vitro and in vivo. By analyzing the gene expression profiles of NeuPs, we also identified NeuP stage-specific genes and characterized patterns of gene regulation throughout granulopoiesis. Importantly, we found that NeuPs have the potential to proliferate, but the proliferation decreased in multiple different hematopoietic stress settings, indicating that proliferating NeuPs are poised at a critical step to regulate granulopoiesis. Our findings will facilitate understanding how the hematopoietic system maintains homeostasis and copes with the demands of granulopoiesis.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
authors.forename: Min-Hyeok
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
authors.forename: Dongchan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
authors.forename: Mirang
authors.initials: M
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
authors.forename: Suk-Jo
authors.initials: SJ
authors.lastname: Kang
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D042381:Granulocyte Precursor Cells / Q000166:cytology* / Q000378:metabolism; D019891:Leukopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C526827:Ly6 protein, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor