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Genomic characterization of murine monocytes reveals C/EBP{beta} transcription factor dependence of Ly6C(-) cells

Item Type:Article
Title:Genomic characterization of murine monocytes reveals C/EBP{beta} transcription factor dependence of Ly6C(-) cells
Creators Name:Mildner, A. and Schoenheit, J. and Giladi, A. and David, E. and Lara-Astiaso, D. and Lorenzo-Vivas, E. and Paul, F. and Chappell-Maor, L. and Priller, J. and Leutz, A. and Amit, I. and Jung, S.
Abstract:Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C(+) monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C(-) monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and transplantation experiments confirmed homeostatic default differentiation of Ly6C(+) into Ly6C(-) monocytes. The main two subsets were homogeneous, but linked by a more heterogeneous differentiation intermediate. We show that monocyte differentiation occurred through de novo enhancer establishment and activation of pre-established (poised) enhancers. Generation of Ly6C(-) monocytes involved induction of the transcription factor C/EBP{beta} and C/EBP{beta}-deficient mice lacked Ly6C(-) monocytes. Mechanistically, C/EBP{beta} bound the Nr4a1 promoter and controlled expression of this established monocyte survival factor.
Keywords:Biomarkers, Bone Marrow Cells, CCAAT-Enhancer-Binding Protein-beta, Cell Differentiation, Cluster Analysis, Gene Expression Profiling, Gene Expression Regulation, Genetic Epigenesis, Genetic Promoter Regions, Genomics, Group A, High-Throughput Nucleotide Sequencing, Immunophenotyping, Knockout Mice, Ly Antigens, Member 1, Monocyte-Macrophage Precursor Cells, Monocytes, Nuclear Receptor Subfamily 4, Phenotype, Protein Binding, Animals, Mice
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press (U.S.A.)
Volume:46
Number:5
Page Range:849-862.e7
Date:16 May 2017
Official Publication:https://doi.org/10.1016/j.immuni.2017.04.018
PubMed:View item in PubMed

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