title: Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate.
abstract: Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chimonocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Briseño
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Grajales-Reyes
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Malay
authors.initials: M
authors.lastname: Haldar
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kretzer
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Wumesh
authors.initials: W
authors.lastname: Kc
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110; kmurphy@wustl.edu.|Howard Hughes Medical Institute, School of Medicine, Washington University, St. Louis, MO 63110.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019070:Cell Lineage; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000235:genetics* / Q000502:physiology*
chemical_list: C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2; C045073:Cre recombinase; D019426:Integrases
keywords: monocyte; plasmacytoid dendritic cell; transcription factor