PMID- 27930303 OWN - NLM STAT- MEDLINE DCOM- 20180413 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 113 IP - 51 DP - 2016 Dec 20 TI - Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate. PG - 14775-14780 LID - 10.1073/pnas.1611408114 [doi] AB - 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-6C(hi) 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. FAU - Wu, Xiaodi AU - Wu X AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Briseno, Carlos G AU - Briseno CG AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Grajales-Reyes, Gary E AU - Grajales-Reyes GE AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Haldar, Malay AU - Haldar M AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Iwata, Arifumi AU - Iwata A AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Kretzer, Nicole M AU - Kretzer NM AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Kc, Wumesh AU - Kc W AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Tussiwand, Roxane AU - Tussiwand R AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Higashi, Yujiro AU - Higashi Y AD - Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan. FAU - Murphy, Theresa L AU - Murphy TL AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110. FAU - Murphy, Kenneth M AU - Murphy KM AD - Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO 63110; kmurphy@wustl.edu. AD - Howard Hughes Medical Institute, School of Medicine, Washington University, St. Louis, MO 63110. LA - eng GR - F31 CA189491/CA/NCI NIH HHS/United States GR - K08 AI106953/AI/NIAID NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - UL1 TR000448/TR/NCATS NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20161205 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (ZEB2 protein, mouse) RN - 0 (Zinc Finger E-box Binding Homeobox 2) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Animals MH - Bone Marrow/metabolism MH - CD8-Positive T-Lymphocytes/cytology MH - Cell Lineage MH - Cytoplasm/metabolism MH - Dendritic Cells/*cytology MH - Female MH - Flow Cytometry MH - Gene Deletion MH - Gene Expression Profiling MH - *Gene Expression Regulation MH - Inflammation MH - Integrases/metabolism MH - Male MH - Mice MH - Monocytes/*cytology MH - Neutrophils/cytology/metabolism MH - Zinc Finger E-box Binding Homeobox 2/*genetics/*physiology PMC - PMC5187668 OTO - NOTNLM OT - monocyte OT - plasmacytoid dendritic cell OT - transcription factor COIS- The authors declare no conflict of interest. EDAT- 2016/12/09 06:00 MHDA- 2018/04/14 06:00 PMCR- 2016/12/05 CRDT- 2016/12/09 06:00 PHST- 2016/12/09 06:00 [pubmed] PHST- 2018/04/14 06:00 [medline] PHST- 2016/12/09 06:00 [entrez] PHST- 2016/12/05 00:00 [pmc-release] AID - 1611408114 [pii] AID - 201611408 [pii] AID - 10.1073/pnas.1611408114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):14775-14780. doi: 10.1073/pnas.1611408114. Epub 2016 Dec 5.