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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Sun, Jiafang Coleman, William G. DiRago, Ladina Ng, Ashley P. Morse, Herbert C. Yoshimi, Ryusuke Wang, Hongsheng Yan, Ming Nutt, Stephen L. Ozato, Keiko Metcalf, Donald Jain, Shweta Abolfath, Sanaz Momben |
Description | Author Affiliation: Wang H ( Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852); Yan M ( Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892); Sun J ( Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852); Jain S ( Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852); Yoshimi R ( Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan); Abolfath SM ( Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852); Ozato K ( Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892); Coleman WG ( Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892); Ng AP ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Metcalf D ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); DiRago L ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Nutt SL ( Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia); Morse HC ( Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852) |
Abstract | The IFN regulatory factor family member 8 (IRF8) regulates differentiation of lymphoid and myeloid lineage cells by promoting or suppressing lineage-specific genes. How IRF8 promotes hematopoietic progenitors to commit to one lineage while preventing the development of alternative lineages is not known. In this study, we report an IRF8-EGFP fusion protein reporter mouse that revealed previously unrecognized patterns of IRF8 expression. Differentiation of hematopoietic stem cells into oligopotent progenitors is associated with progressive increases in IRF8-EGFP expression. However, significant induction of IRF8-EGFP is found in granulocyte-myeloid progenitors and the common lymphoid progenitors but not the megakaryocytic-erythroid progenitors. Surprisingly, IRF8-EGFP identifies three subsets of the seemingly homogeneous granulocyte-myeloid progenitors with an intermediate level of expression of EGFP defining bipotent progenitors that differentiation into either EGFP(hi) monocytic progenitors or EGFP(lo) granulocytic progenitors. Also surprisingly, IRF8-EGFP revealed a highly heterogeneous pre-pro-B population with a fluorescence intensity ranging from background to 4 orders above background. Interestingly, IRF8-EGFP readily distinguishes true B cell committed (EGFP(int)) from those that are noncommitted. Moreover, dendritic cell progenitors expressed extremely high levels of IRF8-EGFP. Taken together, the IRF8-EGFP reporter revealed previously unrecognized subsets with distinct developmental potentials in phenotypically well-defined oligopotent progenitors, providing new insights into the dynamic heterogeneity of developing hematopoietic progenitors. |
ISSN | 00221767 |
e-ISSN | 15506606 |
DOI | 10.4049/jimmunol.1301939 |
Journal | The Journal of Immunology |
Issue Number | 4 |
Volume Number | 193 |
Language | English |
Publisher | The American Association of Immunologists |
Publisher Date | 2014-08-15 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Interferon Regulatory Factors Genetics Lymphopoiesis Immunology Myelopoiesis Animals B-lymphocytes Cytology Cell Differentiation Cell Lineage Genes, Reporter Genotype Granulocyte Colony-stimulating Factor Pharmacology Granulocyte-macrophage Colony-stimulating Factor Granulocytes Green Fluorescent Proteins Hematopoietic Stem Cells Biosynthesis Interleukin-3 Macrophage Colony-stimulating Factor Macrophages Mice Mice, Inbred C57bl Myeloid Cells Recombinant Fusion Proteins T-lymphocytes Research Support, N.i.h., Extramural Research Support, N.i.h., Intramural Research Support, Non-u.s. Gov't Discipline Immunology |
Content Type | Text |
Resource Type | Article |
Subject | Immunology and Allergy Immunology |
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