RRC ID 88196
Author Wu X, Briseño CG, Grajales-Reyes GE, Haldar M, Iwata A, Kretzer NM, Kc W, Tussiwand R, Higashi Y, Murphy TL, Murphy KM.
Title Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate.
Journal Proc Natl Acad Sci U S A
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-6Chi monocytes 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.
Volume 113(51)
Pages 14775-14780
Published 2016-12-20
DOI 10.1073/pnas.1611408114
PII 1611408114
PMID 27930303
PMC PMC5187668
MeSH Animals Bone Marrow / metabolism CD8-Positive T-Lymphocytes / cytology Cell Lineage Cytoplasm / metabolism Dendritic Cells / cytology* Female Flow Cytometry Gene Deletion Gene Expression Profiling Gene Expression Regulation* Inflammation Integrases / metabolism Male Mice Monocytes / cytology* Neutrophils / cytology Neutrophils / metabolism Zinc Finger E-box Binding Homeobox 2 / genetics* Zinc Finger E-box Binding Homeobox 2 / physiology*
IF 9.412
Resource
Mice RBRC01924